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PTSS4246SN16759.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/1101L4AIL01.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/981L1AIL05.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/PTSS4026SN15344_140212235139.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/1101L3AIL03.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/PTSS4026SN15344.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/954L1AIL07.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/961L2AIL03.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/1101L1AIL00.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/PTSS4026SN15336.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/981L4AIL06.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/981L2AIL03.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/PT4026.zipftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/PT954-PT1142.zipftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281/PT4246.zipprimaryOK200003310ailamond@dundee.ac.ukVackar AfzalMass SpectrometryShotgun proteomicsNot availableHumanU2osKeratinocytesPkcTimecoursehttp://www.ebi.ac.uk/pride/archive/projects/PXD003281Whole BodyKeratinocyteA pre-confluent keratinocyte culture was split into two separate cultures with FAD-lysine-arginine medium (Sigma) differentially supplemented either with K0R0 or with K8R10 (stable isotopes of amino acids Lysine and Arginine (Cambridge Isotope Laboratories)). Serum used for the SILAC medium was also depleted for Lysine and Arginine (Sigma). Cells were grown in the SILAC medium for 5-6 days to reach 70 – 80% confluence and later harvested for downstream assays. For measurement of protein abundance changes by SILAC, lysates containing ~80 μg protein were prepared in LDS sample buffer containing reducing agent (TCEP). Proteins were separated by electrophoresis on a 4-12% Bis-Tris NuPAGE gel, which was Coomassie-stained and cut into eight equally sized gel slices. Gel-embedded proteins were reduced with TCEP, alkylated with iodoacetamide, and trypsin-digested to release peptides. Peptides were extracted from gels using 50% acetonitrile (ACN) containing 5% formic acid (FA), dried and resuspended in 5% FA. Peptides were then analysed by LC-MS/MS on a Dionex RSLCnano coupled to a Q-Exactive Orbitrap classic instrument. Specifically, peptides were loaded onto a PepMap100 75μm x 2cm trap column, which was then brought in-line with a 75μm x 50cm PepMap-C18 column and eluted using a linear gradient over 220 min at a constant flow rate of 200 nl/min. The gradient composition was 5% to 35% B, where solvent A = 2% ACN + 0.1% FA and solvent B = 80% ACN + 0.1%FA. Peptides were eluted with a linear elution gradient (5% B to 35% B) over 220 min with a constant flow rate of 200 nl/min. An initial MS scan of 70,000 resolution was acquired, followed by data-dependent MS/MS by HCD on the top 10 most intense ions of ≥2+ charge state at 17,500 resolution. For phosphoenrichment analysis, lysates containing ~2 mg of protein were chloroform:methanol precipitated. Pellets were resuspended in 8M urea in digest buffer (0.1 M Tris pH 8 + 1 mM CaCl2), diluted to 4 M urea with additional digest buffer, and digested with Lys-C for 4h at 37°C. The digests were diluted to 1M urea and trypsin-digested overnight at 37°C. Digests were then acidified and desalted using SepPak-C18 vacuum cartridges. Desalted peptides were resuspended in mobile phase A for HILIC (80% ACN + 0.1% TFA). HILIC chromatography was performed using a Dionex Ultimate 3000 with a TSK Biosciences Amide-80 column (250 x 4.6 mm) (33-35). Peptides were eluted using an exponential gradient (80% B to 60% B) composed of A (above) and B (0.1% TFA) at 0.4 ml/min over 60 min. 16 fractions were collected from 25 min to 60 min. These fractions are enriched for hydrophilic peptides, including phosphopeptides. The fractions were dried before further phosphoenrichment by titanium dioxide (TiO2). For TiO2 enrichment, HILIC fractions were resuspended in loading buffer (70% ACN + 0.3% lactic acid + 3% TFA). 1.25 mg of TiO2 (GL Sciences) was added to each fraction and incubated for 10 min to bind phosphopeptides. Beads were washed with loading buffer, and two wash buffers, composed of (1) 70% ACN + 3% TFA and (2) 20% ACN + 0.5% TFA. Phosphopeptides were eluted in two steps, first with 4% of ammonium hydroxide solution (28% w/w NH3) in water for 1h and again with 2.6% of ammonium hydroxide solution in 50% ACN overnight. Elutions were collected, dried, resuspended in 5% FA and analysed by LC-MS/MS. The LC-MS analysis was performed similarly to above with the following modifications: peptides were chromatographed on an EasySpray PepMap 75 μm x 50 cm column, and a ‘Top30’ method was used where the top 30 most intense ions were chosen for MS/MS fragmentation.PrideSILACiodoacetamide derivatized residuedeaminated residuemonohydroxylated residueacetylated residueA pre-confluent keratinocyte culture was split into two separate cultures with FAD-lysine-arginine medium (Sigma) differentially supplemented either with K0R0 or with K8R10 (stable isotopes of amino acids Lysine and Arginine (Cambridge Isotope Laboratories)). Serum used for the SILAC medium was also depleted for Lysine and Arginine (Sigma). Cells were grown in the SILAC medium for 5-6 days to reach 70 – 80% confluence and later harvested for downstream assays. For measurement of protein abundance changes by SILAC, lysates containing ~80 μg protein were prepared in LDS sample buffer containing reducing agent (TCEP). Proteins were separated by electrophoresis on a 4-12% Bis-Tris NuPAGE gel, which was Coomassie-stained and cut into eight equally sized gel slices. Gel-embedded proteins were reduced with TCEP, alkylated with iodoacetamide, and trypsin-digested to release peptides. Peptides were extracted from gels using 50% acetonitrile (ACN) containing 5% formic acid (FA), dried and resuspended in 5% FA. Peptides were then analysed by LC-MS/MS on a Dionex RSLCnano coupled to a Q-Exactive Orbitrap classic instrument. Specifically, peptides were loaded onto a PepMap100 75μm x 2cm trap column, which was then brought in-line with a 75μm x 50cm PepMap-C18 column and eluted using a linear gradient over 220 min at a constant flow rate of 200 nl/min. The gradient composition was 5% to 35% B, where solvent A = 2% ACN + 0.1% FA and solvent B = 80% ACN + 0.1%FA. Peptides were eluted with a linear elution gradient (5% B to 35% B) over 220 min with a constant flow rate of 200 nl/min. An initial MS scan of 70,000 resolution was acquired, followed by data-dependent MS/MS by HCD on the top 10 most intense ions of ≥2+ charge state at 17,500 resolution. For phosphoenrichment analysis, lysates containing ~2 mg of protein were chloroform:methanol precipitated. Pellets were resuspended in 8M urea in digest buffer (0.1 M Tris pH 8 + 1 mM CaCl2), diluted to 4 M urea with additional digest buffer, and digested with Lys-C for 4h at 37°C. The digests were diluted to 1M urea and trypsin-digested overnight at 37°C. Digests were then acidified and desalted using SepPak-C18 vacuum cartridges. Desalted peptides were resuspended in mobile phase A for HILIC (80% ACN + 0.1% TFA). HILIC chromatography was performed using a Dionex Ultimate 3000 with a TSK Biosciences Amide-80 column (250 x 4.6 mm) (33-35). Peptides were eluted using an exponential gradient (80% B to 60% B) composed of A (above) and B (0.1% TFA) at 0.4 ml/min over 60 min. 16 fractions were collected from 25 min to 60 min. These fractions are enriched for hydrophilic peptides, including phosphopeptides. The fractions were dried before further phosphoenrichment by titanium dioxide (TiO2). For TiO2 enrichment, HILIC fractions were resuspended in loading buffer (70% ACN + 0.3% lactic acid + 3% TFA). 1.25 mg of TiO2 (GL Sciences) was added to each fraction and incubated for 10 min to bind phosphopeptides. Beads were washed with loading buffer, and two wash buffers, composed of (1) 70% ACN + 3% TFA and (2) 20% ACN + 0.5% TFA. Phosphopeptides were eluted in two steps, first with 4% of ammonium hydroxide solution (28% w/w NH3) in water for 1h and again with 2.6% of ammonium hydroxide solution in 50% ACN overnight. Elutions were collected, dried, resuspended in 5% FA and analysed by LC-MS/MS. The LC-MS analysis was performed similarly to above with the following modifications: peptides were chromatographed on an EasySpray PepMap 75 μm x 50 cm column, and a ‘Top30’ method was used where the top 30 most intense ions were chosen for MS/MS fragmentation. Description of the Data Analysis Methods: Raw data was then processed using MaxQuant, which implements the Andromeda search engine, for peptide and protein identification and SILAC quantitation. As the data were collected over several years, several MaxQuant versions were used as follows (raw file labels in parentheses): 1.5.0.0 (PT4246), 1.3.0.5 (PT4026), 1.2.2.5 (PT954, PT961, PT981, PT1101, PT1142). To identify differentially expressed proteins between time 0 and 4, 8 and 12h we collected per time point the proteins whose absolute ratios were >0.5. For each time point, the proteins were then split whether the ratio was positive or negative. 6 lists were annotated for GO terminology using GeneSpring. The extensive list of GO-terms was submitted to Revigo (36) to reduce complexity and the resulting GO-categories depicted in fig. S4. In order to evaluate the correlation between transcriptomics and proteomics we matched the 1155 significant proteins to their counterpart transcripts. Only fold hanges to 0h (respectively for transcripts or proteins) were considered into the analysis. All data was merged into a matrix and analysed using Hopach library in RProteomicsAngus LamondQ ExactivePrinciple InvestigatorPARTIALHomo Sapiens (human)v.z.afzal@dundee.ac.uk29043977 Mishra A, Oulès B, Pisco AO, Ly T, Liakath-Ali K, Walko G, Viswanathan P, Tihy M, Nijjher J, Dunn SJ, Lamond AI, Watt FM. A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis. Elife. 2017 6 10.7554/eLife.27356BiologicalSchool of Life SciencesEpidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states, termed commitment, is poorly understood. Here, we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA - promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis.Mishra Ajay A, Oulès Bénédicte B, Pisco Angela Oliveira AO, Ly Tony T, Liakath-Ali Kifayathullah K, Walko Gernot G, Viswanathan Priyalakshmi P, Tihy Matthieu M, Nijjher Jagdeesh J, Dunn Sara-Jane SJ, Lamond Angus I AI, Watt Fiona M FMsodium salt, Methane, CPD photolyase activity, ammonium formate, 13C-labeled, MeCN, cadmium salt, PhrB photolyase activity, ion, Lysine Hydrochloride, Laboratory, brookite, 2-Hydroxy-, magnesium formate, Basodexan, X-50, zinc salt, CG5925, Solvent, trichloro-, dmTAF[[II]]230, Polypeptides, protein polypeptide chains, Lysine Acetate, cobalt(II) formate dihydrate, CH3-C#N, Cultural, B1, Urea, 2, 3, titanium white, 4, NUP96, outer pigmented layer of retina, 9, epithelium, L Lysine, ethnicity, (S)-2-amino-5-guanidinopentanoic acid, Divorced, amino acids, C79325, TFIID TAF250, K, cel, DmelCG13176, weight-weight percentage, R, Arginine, ORF19, composition, Monohydrate DL-Arginine Acetate, proteins, Divorces, CaCl2, L Lactic Acid, PNCA2, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, 15-disilaoctadecane, pigment epithelium of retina, decreased, LYS, column, desatF-alpha, 3-propanediol, Lysin, ACN, sample, Acn, D1, keratinized cell of epidermis, pigmented retina epithelium, AD3, CT, z, nickel salt, Calcium chloride anhydrous, Sarcolactic Acid, LC-MS2, dTAF[[II]]230, subdivided, cobalt (+2) salt, Trypsin/K, familial, Ct, TAF200, arginine, not genetically inherited, alpha-amino carboxylic acids, BEST:SD05462, Cultural Background, sodium (4:1:1) salt, 11-tetrathia-4, Cultures, magnesium salt, Dm1, anon-WO0118547.726, Emt, LACTIC ACID, dipyrimidine photolyase (photosensitive), anon-WO0118547.730, 1110049F14Rik, D Lactic Acid, Hydrogen Oxide, forked, Acid, divided, Amino acids, instrument, E2IG4, E2ig4, D-Milchsaeure, content, formate, cromium (+3), alpha, septate, beta Trypsin, w/w, desat-2, Desat1, Desat2, Taf250, liquid chromatography-tandem mass spectroscopy, spirit of wood, AI536462, ammonium (4:1) salt, Acids, methyl cyanide, lead (+2) salt, MGO3, (2R)-2-hydroxypropanoic acid, Methyl Alcohol, TAF230, Tcsk, l(1)VE614, nickel formate dihydrate, GLM3, lead formate, fractured, 2 Hydroxypropionic Acid, CG5887, aluminum salt, CH3OH, Carbamide, Amide, protein-containing complex, deoxyribodipyrimidine photolyase activity, CG7826, Propanoic Acid, stratum pigmentosum retinae, Electrophoreses, (2S)-, anatase, LC-MSMS, Gene Products, CG7835, CG42273, Lysine, Carmol, FA-D2, Backgrounds, iones., dTAF[[II]]250, FAM39E, desatF, Acinus, thallium (+1) salt, cell, LRRC54, CG7923, beta-Trypsin, rubidium salt, F23A5.3, Ammonium Lactate, Cultural Relativisms, Sciences, food additive E171, methanoic acid, ions, kf, Solution, acinusL, dTAF250, acinusS, FANCB, FANCD, Customs, L-Arg, peptidos, Chromatographies, Hydroxide, PTHB1, ds2, ds1, constant, mass percentage, 1-(14)C-labeled, (-)-lactic acid, Proteins, split, Methyl alcohol, alpha-amino acids, BG:DS00004.13, potassium formate, copper (+2) salt, Cultural Backgrounds, compositionality, L-Isomer, acetonitrile, buffer, Cell, mKIAA0670, S182, dTAF230, polypeptide, Wash2, DmelCG5887, Wash1, native protein, L-Isomer Arginine, carbonyldiamide, Acetate, C18, cupric formate, Tsk, TSK, chemical analysis, hemorrhaged, TAF[[II]]250/230, Sodium, MeOH, aluminum formate, L-Lysine, AU015151, torn, Taf[[II]]250, AU020952, RPE, lithium formate, Fib-1, underdeveloped, Separations, (2S)-2-amino-5-guanidinopentanoic acid, Bis-Tris, ethanenitrile, MGOUN3, Keratinocyte, retinal pigment epithelium, p. pigmentosa retinae, ME-IV, plan specification, Gene Proteins, DmelCG7923, (2R)-, structure, Relativisms, liquid chromatography tandem mass spectrometry, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Relativism, Cultural Relativism, Enisyl, Methoxide, liquid chromatography tandem mass spectroscopy, D-2-Hydroxypropanoic acid, L-Lactic Acid, NCMe, determination, L-arginine, DL-Arginine Acetate, Blood, Aminosaeure, instrument configuration, zinc formate, Amino acid, Monohydrate, D-Lactic Acid, lead salt, protein, Serum, pigmented epithelium, clefted, composed of, 10, peptide, Cut, nano-TiO2, Background, 15, ammonium tetraformate, peptido, BANF, l(1)7Ba, l(1)7Bb, NH2(-), azanide, Min, BROVCA2, Arg, protein aggregate, present in fewer numbers in organism, DmelCG42273, wood alcohol, LCMSMS, FAD1, FAD2, peptides, BRCC2, Titania, (R)-(-)-lactic acid, 2-Hydroxypropionic Acid, E927b, 2610036I19Rik, (S)-2-Amino-5-guanidinovaleric acid, 2610510L13Rik, pigmented retina, hypoplasia, epsilon-diaminocaproic acid, min, B430209H23, mAPC, copper, SCAN, DNA cyclobutane dipyrimidine photolyase activity, CG11387, rutile, fSAP152, fad2, lithium salt, nano-anatase, desat, Sodium Methoxide, ammonium (2:1) salt, FACD, L-Arginin, PRE, amides, Alzheimer disease, Alcohol, Aminokarbonsaeure, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, PS1, Arginine Hydrochloride, LC-MS/MS, Dmel_CG7826, pigmented retinal epithelium, 7-11HD, Blood Serum, TAFII-250, TAF250/230, fragmented, ur, carbamide, TAFII250, DmelCG5925, HCD, retinal pigment, Ionen, D-2-Hydroxypropionic acid, lysine, TONSOKU, XRCC11, BcDNA:GH10590, WASH, nickel (+2) salt, Carbinol, retinal pigment layer, Dmel_CG7835, 15-tetraethoxy-, carbinol, L-Arginine, Mnb, MNB, PS-1, Amino Acid, ammonium salt, calcium chloride, retinal pigmented epithelium, anatase titanium dioxide, cracked, 2-Hydroxypropanoic Acid, cobaltous formate, BRU1, FA4, AW124434, CG17603, TAF[[II]], Trichloromethane, 9530051K01Rik, METHANOL, phr A photolyase activity, Wood, H2NC(O)NH2, DNA-photoreactivating enzyme, FAD, Fad, SR3-5, Acetamide, copper salt, 2-(bis(2-hydroxyethyl)amino)-2(hydroxymethyl)-1, Polypeptide, D-Lactic acid, GARD:0000632, 1728, Ammonium, malpighian cell, Beliefs, d230, fad, cesium salt, Aminocarbonsaeure, L Isomer, Gene, dTAFII250, Methyl, 2-(1-benzyl-4-methylpyrazol-3-yloxy)-2-methylpropionic acid, alpha-amino acid, ACINUS, photoreactivating enzyme activity, Methylalkohol, Lrrc54, EfW1, LC-MS-MS, L-(+)-arginine, Buffer, formic acid, Karbamid, method, potassium salt, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, polypeptide chain, reduced, dmTAF1, Taf230, subnumerary, mixt. with silica, 14C-labeled, p63, method used in an experiment, Harnstoff, p65, Wood Alcohol, stratum pigmentosa retinae, FANCD1, tiny, Separated, desat2/Fad, TAF250, calcium dichloride, Taf200, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, PRECOCIOUS, BB137857, iones, uniform, Taf1p, methanol, decreased number, calcium formate, calcium chloride anhydrous, DmelCG11387, wood naphtha, cromium (+3) salt, amide, l(3)S028813, culture, TAF, bis(2-hydroxyethyl)imino-tris(hydroxymethyl)methane, F23A5_3, 2-iodo-, sodium formate, TCEP, small, DYRK1, data, Lactate, TAF[[II]]250, 2 Hydroxypropanoic Acid, nickel formate, 3H-labeled, protein complex, BRUSHY1, dihydridonitrate(1-), strontium formate, l(3)84Ab, titanium oxide, strontium salt, DL Arginine Acetate, Peptide, Methanol, Belief, Isotope, stratum pigmentosum (retina), MODIFIER OF SNC1, LC/MS/MS, Phosphopeptide, natural protein, p230, 16-Dioxa-8, Protein, deoxyribonucleic photolyase activity, Hydrochloride, D-lactic acid, TFIID, L Arginine, Dyrk1, Vacuums, ACETONITRILE, cyanomethane, CG13176, 2410150O07Rik, Separation, TAF[[II]]230, photolyase activity, uree, urea, CC1, Tripcellim, TAF[II]250, Amino, sample population, chromic formate, UREA, Protein Gene Products, incised, Trypure, DmelCG17603, Ion, wood spirit, [CaCl2], calcium salt, Peptid, assay, 6-diaminohexanoic acid, SCH, Serums, TAF1vertebrate epidermis, Dual specificity phosphatase 19, human being, skin, Dual-specificity phosphatase TS-DSP1, epidermis., Dual-specificity protein phosphatase 19, epidermis (sensu Metazoa), outer epidermal layer, outer epithelial layer, hypodermis, Protein phosphatase, hypoderm, man, incidence, human, temporal, isoform CRA_asodium salt, Methane, CPD photolyase activity, ammonium formate, Library., 13C-labeled, MeCN, cadmium salt, PhrB photolyase activity, ion, Raw, Lysine Hydrochloride, Laboratory, Ass-1, brookite, 2-Hydroxy-, magnesium formate, Basodexan, X-50, zinc salt, CG5925, Solvent, trichloro-, Long Term, dmTAF[[II]]230, Polypeptides, protein polypeptide chains, Lysine Acetate, cobalt(II) formate dihydrate, Method, CH3-C#N, Cultural, B1, Urea, fold, 2, 3, titanium white, 4, NUP96, Analysis, outer pigmented layer of retina, 9, epithelium, L Lysine, ethnicity, (S)-2-amino-5-guanidinopentanoic acid, Divorced, amino acids, C79325, TFIID TAF250, Analyses, K, cel, DmelCG13176, weight-weight percentage, R, AI844555, Arginine, ORF19, composition, Monohydrate DL-Arginine Acetate, proteins, Divorces, CaCl2, procedures, L Lactic Acid, PNCA2, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, 15-disilaoctadecane, pigment epithelium of retina, decreased, LYS, column, desatF-alpha, 3-propanediol, Lysin, ACN, sample, Acn, D1, keratinized cell of epidermis, pigmented retina epithelium, AD3, CT, z, nickel salt, Calcium chloride anhydrous, Sarcolactic Acid, LC-MS2, dTAF[[II]]230, subdivided, cobalt (+2) salt, Trypsin/K, familial, Ct, TAF200, Longterm Effect, arginine, Procedure, not genetically inherited, alpha-amino carboxylic acids, BEST:SD05462, Cultural Background, sodium (4:1:1) salt, 11-tetrathia-4, Nomenclature, Cultures, magnesium salt, Dm1, anon-WO0118547.726, Emt, LACTIC ACID, dipyrimidine photolyase (photosensitive), anon-WO0118547.730, 1110049F14Rik, D Lactic Acid, Hydrogen Oxide, forked, Acid, divided, Amino acids, instrument, E2IG4, E2ig4, D-Milchsaeure, content, formate, proportionality, cromium (+3), rate, alpha, Methodological, septate, beta Trypsin, w/w, desat-2, Desat1, Desat2, Taf250, liquid chromatography-tandem mass spectroscopy, spirit of wood, AI536462, ammonium (4:1) salt, Acids, methyl cyanide, lead (+2) salt, MGO3, (2R)-2-hydroxypropanoic acid, Methyl Alcohol, TAF230, Tcsk, l(1)VE614, nickel formate dihydrate, GLM3, lead formate, Effects, Peptidomics, fractured, 2 Hydroxypropionic Acid, CG5887, aluminum salt, CH3OH, Carbamide, Amide, protein-containing complex, deoxyribodipyrimidine photolyase activity, CG7826, Propanoic Acid, stratum pigmentosum retinae, period, Electrophoreses, (2S)-, anatase, LC-MSMS, Gene Products, CG7835, CG42273, Lysine, Carmol, FA-D2, Technique, Backgrounds, DmelCG7615, proportion, dTAF[[II]]250, FAM39E, desatF, Acinus, thallium (+1) salt, Longterm, cell, LRRC54, CG7923, beta-Trypsin, rubidium salt, F23A5.3, Ammonium Lactate, Cultural Relativisms, Sciences, food additive E171, Long-Term, methanoic acid, ions, kf, Solution, acinusL, Study, dTAF250, acinusS, FANCB, FANCD, Customs, L-Arg, peptidos, Chromatographies, Hydroxide, PTHB1, ds2, ds1, constant, mass percentage, 1-(14)C-labeled, (-)-lactic acid, Proteins, split, Methyl alcohol, alpha-amino acids, BG:DS00004.13, potassium formate, copper (+2) salt, Cultural Backgrounds, compositionality, L-Isomer, acetonitrile, buffer, Cell, mKIAA0670, S182, Engine, dTAF230, polypeptide, Wash2, DmelCG5887, Wash1, native protein, L-Isomer Arginine, carbonyldiamide, Acetate, C18, cupric formate, Tsk, TSK, chemical analysis, Long Term Effects, hemorrhaged, TAF[[II]]250/230, Sodium, MeOH, aluminum formate, L-Lysine, AU015151, torn, Taf[[II]]250, AU020952, RPE, lithium formate, Col4a-1, Fib-1, underdeveloped, Separations, (2S)-2-amino-5-guanidinopentanoic acid, Bis-Tris, ethanenitrile, MGOUN3, Keratinocyte, retinal pigment epithelium, Longterm Effects, p. pigmentosa retinae, ME-IV, plan specification, Gene Proteins, DmelCG7923, (2R)-, structure, quotient, CG7615, Relativisms, liquid chromatography tandem mass spectrometry, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Relativism, Cultural Relativism, Enisyl, Data Analyses, Methoxide, liquid chromatography tandem mass spectroscopy, D-2-Hydroxypropanoic acid, L-Lactic Acid, Bru, NCMe, determination, L-arginine, DL-Arginine Acetate, Blood, Aminosaeure, instrument configuration, zinc formate, Amino acid, Monohydrate, D-Lactic Acid, lead salt, protein, Serum, pigmented epithelium, clefted, composed of, 10, peptide, Cut, nano-TiO2, Background, 15, Techniques, ammonium tetraformate, peptido, ClvPrd, BANF, l(1)7Ba, l(1)7Bb, NH2(-), AA408052, azanide, Min, BROVCA2, Arg, protein aggregate, present in fewer numbers in organism, Effect, DmelCG42273, wood alcohol, PIST, Svc, LCMSMS, FAD1, FAD2, peptides, BRCC2, Titania, (R)-(-)-lactic acid, 2-Hydroxypropionic Acid, E927b, 2610036I19Rik, (S)-2-Amino-5-guanidinovaleric acid, 2610510L13Rik, pigmented retina, hypoplasia, epsilon-diaminocaproic acid, min, B430209H23, mAPC, copper, SCAN, DNA cyclobutane dipyrimidine photolyase activity, CG11387, rutile, DEPP, ASS, fSAP152, fad2, lithium salt, Methodological Studies, Fseg, nano-anatase, desat, Sodium Methoxide, time point, ammonium (2:1) salt, Long-Term Effects, FACD, L-Arginin, ratio, PRE, amides, Alzheimer disease, Alcohol, Aminokarbonsaeure, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, PS1, Arginine Hydrochloride, LC-MS/MS, Dmel_CG7826, Search, pigmented retinal epithelium, 7-11HD, Blood Serum, TAFII-250, TAF250/230, fragmented, ur, carbamide, Fasting-induced gene protein, TAFII250, DmelCG5925, HCD, retinal pigment, Ionen, D-2-Hydroxypropionic acid, lysine, TONSOKU, XRCC11, BcDNA:GH10590, WASH, nickel (+2) salt, Carbinol, retinal pigment layer, GOPC1, Dmel_CG7835, 15-tetraethoxy-, carbinol, L-Arginine, Mnb, MNB, PS-1, Amino Acid, ammonium salt, calcium chloride, retinal pigmented epithelium, anatase titanium dioxide, cracked, 2-Hydroxypropanoic Acid, cobaltous formate, BRU1, FA4, AW124434, CG17603, TAF[[II]], Methodological Study, Trichloromethane, 9530051K01Rik, METHANOL, phr A photolyase activity, Wood, H2NC(O)NH2, DNA-photoreactivating enzyme, FAD, Fad, SR3-5, Acetamide, copper salt, 2-(bis(2-hydroxyethyl)amino)-2(hydroxymethyl)-1, Polypeptide, D-Lactic acid, GARD:0000632, 1728, time, Ammonium, malpighian cell, Beliefs, d230, fad, Procedures, cesium salt, Aminocarbonsaeure, L Isomer, Gene, dTAFII250, Methyl, 2-(1-benzyl-4-methylpyrazol-3-yloxy)-2-methylpropionic acid, alpha-amino acid, ACINUS, photoreactivating enzyme activity, Methylalkohol, Lrrc54, EfW1, 2210402P09Rik, LC-MS-MS, L-(+)-arginine, Buffer, formic acid, Karbamid, method, potassium salt, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, polypeptide chain, reduced, dmTAF1, Taf230, subnumerary, mixt. with silica, 14C-labeled, p63, method used in an experiment, Harnstoff, p65, Studies, Wood Alcohol, stratum pigmentosa retinae, Del(8)44H, FANCD1, tiny, Separated, desat2/Fad, TAF250, calcium dichloride, Search Engines, Taf200, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, PRECOCIOUS, BB137857, iones, uniform, Taf1p, methanol, decreased number, calcium formate, calcium chloride anhydrous, DmelCG11387, wood naphtha, cromium (+3) salt, amide, Long-Term Effect, l(3)S028813, culture, TAF, bis(2-hydroxyethyl)imino-tris(hydroxymethyl)methane, F23A5_3, 2-iodo-, sodium formate, TCEP, small, Decidual protein induced by progesterone, DYRK1, data, Lactate, TAF[[II]]250, 2 Hydroxypropanoic Acid, nickel formate, 3H-labeled, protein complex, BRUSHY1, dihydridonitrate(1-), strontium formate, l(3)84Ab, titanium oxide, strontium salt, DL Arginine Acetate, Peptide, Methanol, Belief, Isotope, stratum pigmentosum (retina), MODIFIER OF SNC1, LC/MS/MS, Phosphopeptide, natural protein, p230, 16-Dioxa-8, Protein, deoxyribonucleic photolyase activity, CAL, Hydrochloride, D-lactic acid, TFIID, L Arginine, Dyrk1, Vacuums, techniques, ACETONITRILE, cyanomethane, CG13176, 2410150O07Rik, Separation, TAF[[II]]230, photolyase activity, uree, urea, CC1, Tripcellim, TAF[II]250, Amino, sample population, chromic formate, UREA, dJ94G16.2, Protein Gene Products, incised, Trypure, FIG, DmelCG17603, Ion, Data, wood spirit, [CaCl2], calcium salt, Peptid, assay, 6-diaminohexanoic acid, SCH, Serums, methodology, TAF1Forms, DmErk, extracellular signal-regulated kinase activity, pp44mapk, CG33956, Tyro5, AGL7, D-fos, jra, P270, PTP-HA2, Long Term, p38a, Prp4 protein kinase activity, dmTAF[[II]]230, actin-dependent regulator of chromatin subfamily F member 1, protein polypeptide chains, MKP3, LeMPK3, MKP5, calna1, ATP-protein transphosphorylase activity, PPP2B, p44mpk, ATP:protein phosphotransferase (non-specific) activity, Dp38, SAPK2, primary stem, SEM, Sem, p38A, MAP-k, TFIID TAF250, pp42, cel, EK5, Nonmigrant, AI158871, Dsor2, Age of onset, proteins, V, inhibition of homeostatic process, sem, Transient, stem cell renewal, Jun, JUN, CN, D-Fos, F4N2_9, PNP1, phosphatase, ELD, CALNA1, DmMPK2, ERK-A, p82 kinase activity, hOSA1, jun, dTAF[[II]]230, dpERK, dpErk, D-Jun, ERK-1, ERK-2, betaIIPKC, TAF200, Longterm Effect, DmMAPK, PMK-2, dp-ERK, PMK-1, hPTP1E, PMK-3, FAP-1, Wee-kinase activity, FOS, Fos, D-jun, pMAPK, pMapK, D-MPK2, Migrants and Transients, DmelCG5475, DmERKA, rl/MAPK, fos, OSA1, non-specific serine/threonine protein kinase activity, l(2)41Ac, Mtap2k, human, C78273, CT34260, dpERk, Taf250, primary axis, serine-specific protein kinase activity, SAPK, HIPK2, cytidine 3', Migrants, Fra, RIP, Wee 1-like kinase activity, TAF230, 9030612K14Rik, p44erk1, D-p38 MAPK, APETALA1, glycogen synthase A kinase activity, Effects, cJun, glycogen synthase kinase 3 activity, 12559, fra, DmelCG33956, stalk, CnA, protein-containing complex, Transcription Factor, terminal differentiation, phosphorylase b kinase kinase activity, EK2-1, period, pyst1, AA407128, dMPK2, Prkm1, Prkm3, ribosomal protein S6 kinase II activity, dJRA, dJra, ERK, Erk, PRKM1, PRKM3, PRKM2, protein-serine kinase activity, Transcription, dTAF[[II]]250, p38Ka, Longterm, cell, calcineurin, PCBC, STK32, dJun, dJUN, BAF250, Long-Term, Worker, man, culm, erk, dTAF250, AW413465, DmelCG2275, protein-cysteine kinase activity, BRG1-associated factor 250, transient structure, Hpr kinase activity, negative regulation of homeostatic process, PTP1B, rll, l(2R)IA109, STK26, p38-2, myelin basic protein kinase activity, Dp38a, SMARCF1, DRT, Esrk1, BM029, stress-activated kinase activity, MAP-2 kinase activity, time., BG:DS00004.13, Factor, protein serine kinase activity, PTP-1B, Cell, protein phosphokinase activity, Djun, dTAF230, CNA1, dm-Jun, PKA, Activator protein 1, native protein, PKC, stress-activated protein kinase activity, Calna1, mapk2, Long Term Effects, mapk1, djun, TAF[[II]]250/230, cna1, regulation of homeostatic process, protein kinase p58 activity, PTPL1, DJUN, DJun, serine/threonine protein kinase activity, Taf[[II]]250, MRD14, 1300019I03Rik, Kay, BAF250A, CG12559, c-Fos, dfos, PTPLE, ccn1, P42MAPK, dpERK1, FLORAL HOMEOTIC PROTEIN APETALA1, CG2275, Keratinocyte, dsk1, SWI|SNF complex protein p270, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, Longterm Effects, matrix-associated, AP1, AU018647, 2610306G15Rik, ARID domain-containing protein 1A, dAP-1, dFos, dpMAPK, c-fos, Nomads, DFos, DFOS, p44mapk, protein serine-threonine kinase activity, SAP kinase activity, glycogen synthase kinase activity, D-jun/Jra, protein kinase A activity, AP-1, d-jun, Mpk2, p42mapk, protein, D-p38, CCN1, p38 alpha, SR2-1, BAF250a, Dfos, P44ERK1, DFra, SWI|SNF-related, AI848390, CALNA, kinase-related transforming protein, 2900074D19Rik, mitogen-activated protein kinase activity, protein aggregate, mpk2, mpk1, Effect, Calna, dFra, dFRA, CG15507, CG15509, Erk/Map kinase, Migrant Worker, reference sample, AGAMOUS-like 7, caln, l(2)IA109, DERK-A, E(sina)7, Rl, Raf kinase activity, reaction, MP kinase activity, serine kinase activity, DERK, Dmp38a, atypical protein kinase C activity, F4N2.9, MBP kinase II activity, Squatters, homeostasis, ATP - protein phosphotransferase (MAPKK-activated) activity, mitogen-activated S6 kinase activity, c-Jun, protein-aspartyl kinase activity, dERK, d-fos, CG5475, Long-Term Effects, V-jun avian sarcoma virus 17 oncogene homolog, CALN, MNK1, Mnk1, MAP kinase 2 activity, d-JRA, Mapk, PTP1E, Osa homolog 1, Erk1, ERK1, ERK2, mapk1a, Erk2, TAFII-250, TAF250/230, D-P38a, Ptpri, Caln, M phase-specific cdc2 kinase activity, D-p38a, TAFII250, TA-PP2C, p41mapk, positive regulation of homeostatic process, MapK, mapk1b, MAPK, Migrant, B120, P38, PTP-BAS, Workers, serine protein kinase activity, erk2, mapk, ppp2b, ERKa, phosphorylase B kinase kinase activity, D-fos/kay, Factors, BcDNA:RE08694, protein glutamyl kinase activity, l(2R)EMS45-39, Ptp, CAPB, DmelCG12559, p38, p39, CG17603, TAF[[II]], DpErk, DpERK, ErkA, ERKA, HUMKER1A, hydroxyalkyl-protein kinase activity, WEE1Hu, SR3-5, p41, epsilon PKC, d-Jun, p40, P44MAPK, p44, time, pERK, AI324989, ribosomal S6 protein kinase activity, d230, calcium/phospholipid-dependent protein kinase activity, human being, HH19, GroupII, l(2)46Ef, dTAFII250, EfW1, Migrant Workers, dp38a, hELD, Hek5, HS44KDAP, AH119, polypeptide chain, dmTAF1, Taf230, SWI-like protein, 9130017A15Rik, TAPP2C, serine(threonine) protein kinase activity, p42-MAPK, TAF250, T-antigen kinase activity, fbz, galactosyltransferase-associated kinase activity, Taf200, dlhD, RGD1310383, xp42, Transients, Nonmigrants, Taf1p, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, Squatter, Erk-1, protein kinase (phosphorylating) activity, Suspension, Raf-1, DmERK-A, Long-Term Effect, TAF, casein kinase (phosphorylating) activity, Controlled, Autoregulation, data, Controlling, TAF[[II]]250, ert1, AI841391, Proto-oncogene c-Jun, protein complex, DMPK2, axis, Jun A, prkm2, CT39192, prkm1, l(3)84Ab, calna, p38delta, PTP-BL, twitchin kinase activity, natural protein, p230, group 2, Protein, AP50 kinase activity, MBP kinase I activity, Nomad, TFIID, Xp42, threonine-specific protein kinase activity, C1orf4, TAF[[II]]230, mitogen activated kinase activity, Su(Raf)2B, mkp3, phosphoric monoester hydrolase activity, TAF[II]250, PYST1, EY2-2, MAPK2, MAPK1, Age symptoms begin, dp38, activation of homeostatic process, DmelCG17603, D-ERK, BRG1-associated factor 250a, Ert2, ERT1, ERT2, EPHT3, p44-MAPK, p44-ERK1, AA672638, MKP-3, JRA, MKP-5, MAP kinase 1 activity, A-kinase activity, TAF1Forms, DmErk, extracellular signal-regulated kinase activity, pp44mapk, CG33956, Tyro5, AGL7, D-fos, jra, P270, PTP-HA2, Long Term, p38a, Prp4 protein kinase activity, dmTAF[[II]]230, actin-dependent regulator of chromatin subfamily F member 1, protein polypeptide chains, MKP3, LeMPK3, MKP5, calna1, ATP-protein transphosphorylase activity, PPP2B, p44mpk, ATP:protein phosphotransferase (non-specific) activity, Dp38, SAPK2, primary stem, SEM, Sem, p38A, MAP-k, TFIID TAF250, pp42, cel, EK5, Nonmigrant, AI158871, Dsor2, Age of onset, proteins, V, inhibition of homeostatic process, sem, Transient, stem cell renewal, Jun, JUN, CN, D-Fos, F4N2_9, PNP1, phosphatase, ELD, CALNA1, DmMPK2, ERK-A, p82 kinase activity, hOSA1, jun, dTAF[[II]]230, dpERK, dpErk, D-Jun, ERK-1, ERK-2, betaIIPKC, TAF200, Longterm Effect, DmMAPK, PMK-2, dp-ERK, PMK-1, hPTP1E, PMK-3, FAP-1, Wee-kinase activity, FOS, Fos, D-jun, pMAPK, pMapK, D-MPK2, Migrants and Transients, DmelCG5475, DmERKA, rl/MAPK, fos, OSA1, non-specific serine/threonine protein kinase activity, l(2)41Ac, Mtap2k, human, C78273, CT34260, dpERk, Taf250, primary axis, serine-specific protein kinase activity, SAPK, HIPK2, cytidine 3', Migrants, Fra, RIP, Wee 1-like kinase activity, TAF230, 9030612K14Rik, p44erk1, D-p38 MAPK, APETALA1, glycogen synthase A kinase activity, Effects, cJun, glycogen synthase kinase 3 activity, 12559, fra, DmelCG33956, stalk, CnA, protein-containing complex, Transcription Factor, terminal differentiation, phosphorylase b kinase kinase activity, EK2-1, period, pyst1, AA407128, dMPK2, Prkm1, Prkm3, ribosomal protein S6 kinase II activity, dJRA, dJra, ERK, Erk, PRKM1, PRKM3, PRKM2, protein-serine kinase activity, Transcription, dTAF[[II]]250, p38Ka, Longterm, cell, calcineurin, PCBC, STK32, dJun, dJUN, BAF250, Long-Term, Worker, man, culm, erk, dTAF250, AW413465, DmelCG2275, protein-cysteine kinase activity, BRG1-associated factor 250, transient structure, Hpr kinase activity, negative regulation of homeostatic process, PTP1B, rll, l(2R)IA109, STK26, p38-2, myelin basic protein kinase activity, Dp38a, SMARCF1, DRT, Esrk1, BM029, stress-activated kinase activity, MAP-2 kinase activity, time., BG:DS00004.13, Factor, protein serine kinase activity, PTP-1B, Cell, protein phosphokinase activity, Djun, dTAF230, CNA1, dm-Jun, PKA, Activator protein 1, native protein, PKC, stress-activated protein kinase activity, Calna1, mapk2, Long Term Effects, mapk1, djun, TAF[[II]]250/230, cna1, regulation of homeostatic process, protein kinase p58 activity, PTPL1, DJUN, DJun, serine/threonine protein kinase activity, Taf[[II]]250, MRD14, 1300019I03Rik, Kay, BAF250A, CG12559, c-Fos, dfos, PTPLE, ccn1, P42MAPK, dpERK1, FLORAL HOMEOTIC PROTEIN APETALA1, CG2275, Keratinocyte, dsk1, SWI|SNF complex protein p270, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, Longterm Effects, matrix-associated, AP1, AU018647, 2610306G15Rik, ARID domain-containing protein 1A, dAP-1, dFos, dpMAPK, c-fos, Nomads, DFos, DFOS, p44mapk, protein serine-threonine kinase activity, SAP kinase activity, glycogen synthase kinase activity, D-jun/Jra, protein kinase A activity, AP-1, d-jun, Mpk2, p42mapk, protein, D-p38, CCN1, p38 alpha, SR2-1, BAF250a, Dfos, P44ERK1, DFra, SWI|SNF-related, AI848390, CALNA, kinase-related transforming protein, 2900074D19Rik, mitogen-activated protein kinase activity, protein aggregate, mpk2, mpk1, Effect, Calna, dFra, dFRA, CG15507, CG15509, Erk/Map kinase, Migrant Worker, reference sample, AGAMOUS-like 7, caln, l(2)IA109, DERK-A, E(sina)7, Rl, Raf kinase activity, reaction, MP kinase activity, serine kinase activity, DERK, Dmp38a, atypical protein kinase C activity, F4N2.9, MBP kinase II activity, Squatters, homeostasis, ATP - protein phosphotransferase (MAPKK-activated) activity, mitogen-activated S6 kinase activity, c-Jun, protein-aspartyl kinase activity, dERK, d-fos, CG5475, Long-Term Effects, V-jun avian sarcoma virus 17 oncogene homolog, CALN, MNK1, Mnk1, MAP kinase 2 activity, d-JRA, Mapk, PTP1E, Osa homolog 1, Erk1, ERK1, ERK2, mapk1a, Erk2, TAFII-250, TAF250/230, D-P38a, Ptpri, Caln, M phase-specific cdc2 kinase activity, D-p38a, TAFII250, TA-PP2C, p41mapk, positive regulation of homeostatic process, MapK, mapk1b, MAPK, Migrant, B120, P38, PTP-BAS, Workers, serine protein kinase activity, erk2, mapk, ppp2b, ERKa, phosphorylase B kinase kinase activity, D-fos/kay, Factors, BcDNA:RE08694, protein glutamyl kinase activity, l(2R)EMS45-39, Ptp, CAPB, DmelCG12559, p38, p39, CG17603, TAF[[II]], DpErk, DpERK, ErkA, ERKA, HUMKER1A, hydroxyalkyl-protein kinase activity, WEE1Hu, SR3-5, p41, epsilon PKC, d-Jun, p40, P44MAPK, p44, time, pERK, AI324989, ribosomal S6 protein kinase activity, d230, calcium/phospholipid-dependent protein kinase activity, human being, HH19, GroupII, l(2)46Ef, dTAFII250, EfW1, Migrant Workers, dp38a, hELD, Hek5, HS44KDAP, AH119, polypeptide chain, dmTAF1, Taf230, SWI-like protein, 9130017A15Rik, TAPP2C, serine(threonine) protein kinase activity, p42-MAPK, TAF250, T-antigen kinase activity, fbz, galactosyltransferase-associated kinase activity, Taf200, dlhD, RGD1310383, xp42, Transients, Nonmigrants, Taf1p, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, Squatter, Erk-1, protein kinase (phosphorylating) activity, Suspension, Raf-1, DmERK-A, Long-Term Effect, TAF, casein kinase (phosphorylating) activity, Controlled, Autoregulation, data, Controlling, TAF[[II]]250, ert1, AI841391, Proto-oncogene c-Jun, protein complex, DMPK2, axis, Jun A, prkm2, CT39192, prkm1, l(3)84Ab, calna, p38delta, PTP-BL, twitchin kinase activity, natural protein, p230, group 2, Protein, AP50 kinase activity, MBP kinase I activity, Nomad, TFIID, Xp42, threonine-specific protein kinase activity, C1orf4, TAF[[II]]230, mitogen activated kinase activity, Su(Raf)2B, mkp3, phosphoric monoester hydrolase activity, TAF[II]250, PYST1, EY2-2, MAPK2, MAPK1, Age symptoms begin, dp38, activation of homeostatic process, DmelCG17603, D-ERK, BRG1-associated factor 250a, Ert2, ERT1, ERT2, EPHT3, p44-MAPK, p44-ERK1, AA672638, MKP-3, JRA, MKP-5, MAP kinase 1 activity, A-kinase activity, TAF1vertebrate epidermis, Dual specificity phosphatase 19, human being, skin, Dual-specificity phosphatase TS-DSP1, epidermis., Dual-specificity protein phosphatase 19, epidermis (sensu Metazoa), outer epidermal layer, outer epithelial layer, hypodermis, Protein phosphatase, hypoderm, man, incidence, human, temporal, isoform CRA_a331trueA protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermisEpidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states,termed commitment, is poorly understood. Here we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA – promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment. 2017-10-182015-12-07PXD003281280655164609918049829535851114514621333524422492156843179819354407110946194202452787284218809036809327042933084581058113633363515242601198343006636362758385696363NCBITaxon:1280688885618961114301187263514725557114526314526236493461364031952065126957366649239161974670738538836411354615821582310665903416889539053113636476272112329442229118099555832323122586365458333460792519365914320597129386558195851149315242592637371250232NCBITaxon:127211195774818661968211488584310430024513586722568076175543735925408169180454266834295319453058612668352010891498225058149636744521585545281132081479564100392375146369420494332089643795042089634459741379791387127283844006672032754532602935293671567593880364784346438677160521659940483216597216595455032309813152826930421659156271616968339162432183217546271292042779447623764543121810017203094980197525556978159509329629439843948840479NCBITaxon:21575253381315273551531051067439899037122857759515205968762262311210884555588845587077918178081736309431796758144571698936160488409859NCBITaxon:37162104782679401505907148364320421061320491381693630355543204663263331199456545674535110254111032174592161292886712642012886764100264203694569410167634102107612773515248671316582392547279334281461358430141729876091746334577444916754760489321287356756840301350621917265181301941119294393671104113167342810239320255598632582788396591047594120347495109716049016529982790513355252731336636666681024298036691758543980110243260866310245980875741755518320196447145268012675777641457966313670190832331156114155355104219325552113834396571927634981812359871069955529NCBITaxon:47518502983354761136157414654771800665564843376776020721441379299767982510216998238976414008208407414008211373511557186287011089725482444474153NCBITaxon:505578996984467525100036465349148624633414714749354801946751299114359741276473137081154666326547876565893639835322159589366983819201110677577271034811208370985234878026555414884142228638096647946409860995861571871766859919633715729513722117110129292117527110768783497419860202809134858513485845025392499148840633424951869123423515233598589859886559132497464998703920211107294331171139363527215987419085037117082711708282874341821144522350241451139692931902197822459390774636046147123747226940210195375939723287581721874202532566481219071NCBITaxon:573905079452659600131972211915853101774208588596321387NCBITaxon:61575052102830798951558641105198997237505998971246663576131720002631887634196102642661088878176179212190659407121906772275885815689964975151950582873756269072445066NCBITaxon:250682023717NCBITaxon:1703612201999857050605061724074767927450627249159615333554319313355418400524643213686150596487844612286662941786661347515363291018194301086731018510184NCBITaxon:176357303963558633149246437286287151458670580430801321650852718481865368595105135553482260710185687294296110091416333NCBITaxon:619184023210007348824123363630710470058127187878645159812894555663577553470951451225786425011449447260704NCBITaxon:1335626260705260707573061658457367734054163677483167233150561007133705654195NCBITaxon:3055504457913998781681190119287512987222829126806315327341478281055524NCBITaxon:9606135858469008171929111167815021979153283051930283672859300852900561742NCBITaxon:569382688306401794699138995915101184995262254352587591315159014140129448242838111394422584416041937047592721204414370860423281677285035158199011951953259084126738637013702492405360883858162248839432293653186156227748817562615835583715371633376057267119350199808611935021678791085791371137127240719065037147591713291212266262981288057125627457572701329090309031133355037281424337385794792491007875282411082NCBITaxon:961572433594633185862607991612432141262200298147802492670NCBITaxon:12637192812492125283038568385695911692661006581373530963223756127504542666255151978813566381647520375064422366950236009412934979054632245552536352472140125751511519976499085151514389923745461703747445446415226473243235937602647315920222887051580595536100199955508815793271602938515781149786338924794362938211620894535936479437509173NCBITaxon:68544127542251177529915901090134167387158955210129661030612967142368715851584515849157592376593934141038432715910022637673388914792359046142344423454670012876895911983329661091494467041464792936576164280341160221641331599280382803536909108917688149229990894621812141080348179392464028788929502711313329528282944568617493468191126526997227321890382102862107601247190400727159736997828114311402064119810871355477436581424507229533796982042321242231291632180336982234708714537209164573321535815754626694026561940137165467599287770202060328114319338293550833291292412922114864374572526499972830357390871830872672710379085507176299707678926837041557372921405315628876513882941281607839563924314262654898227377561159253905962073220865958827355516936053307972551811354914321371597495350261159556143213840607258781414473352150949334919496340161433472800593604631646104660762903381518454744850035670974772656691180771951240174841855601335755547920427415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