Single cell RNAseq of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium
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PROVIDER: PRJNA667173 | ENA |
REPOSITORIES: ENA
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Project description:Here, we studied transcriptome profiles of human nail units from polydactly samples. Single cell RNAseq with 11,541 cells from 4 extra digits revealed nail-specific mesenchymal and epithelial cell populations
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Project description:Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees. Nail matrix cells were harvested from proximal and distal matrix region by microdissection and processed to RNA extraction and hybridization on Affymetrix microarrays. We analyzed two proximal and two distal matrix cells.
2013-03-27 | E-GEOD-45494 | biostudies-arrayexpress
Project description:The nail unit and hair follicle are both hard keratin-producing organs that share various biological features. In this study, we demonstrated the presence of a nail-specific mesenchymal population called onychofibroblasts within the onychodermis. Onychodermis and follicular dermal papilla (DP) both expressed WNT and bone morphogenetic protein (BMP) signaling molecules. To analyze the function of BMP5 in nail development, we treated cultured human nail matrix keratinocytes (NMKs) with BMP5, which are highly expressed by onychofibroblasts. We observed increased expressions of hard keratin and HOXC13.
2022-07-02 | GSE193269 | GEO
Project description:Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees.
2013-03-27 | GSE45494 | GEO
Project description:Here, we have asked why the nail base is essential for mammalian digit tip regeneration, focusing on the inductive nail mesenchyme. We identify a transcriptional signature for these cells that includes Lmx1b, and show that the Lmx1b-expressing nail mesenchyme is essential for blastema formation. We use a combination of Lmx1bCreERT2-based lineage tracing and single cell transcriptional analyses to show that the nail mesenchyme contributes cells for two pro-regenerative mechanisms. One group of cells maintains their identity and regenerates the new nail mesenchyme. A second group contributes specifically to the dorsal blastema, loses their nail mesenchyme phenotype, acquires a blastema transcriptional state that is highly similar to blastema cells of other origins and ultimately contributes to regeneration of the dorsal but not ventral dermis and bone. Thus, the regenerative necessity for an intact nail base is explained, at least part by a requirement for the inductive nail mesenchyme.
2022-11-16 | GSE217600 | GEO
Project description:Numerous single gene mutations identified in humans and mice result in nail deformities with many similarities between the species. A spontaneous, autosomal, recessive mutation called witch nails whnl is described here where the distal nail matrix and nail bed undergo degenerative changes resulting in formation of an abnormal nail plate causing mice to develop long, curved nails. This mutation arose spontaneously in a colony of MRL MpJ-Faslpr J at The Jackson Laboratory. Homozygous mutant mice are recognizable by 8 weeks of age by their long, curved nails. The whnl mutation, mapped on Chromosome 15, is due to a 7-bp insertion identified in the 3 region of exon 9 in the Krt90 gene formerly Riken cDNA 4732456N10Rik, and is predicted to result in a frameshift that changes serine 476 to arginine and subsequently introduces 36 novel amino acids into the protein before a premature stop codon p. Ser476ArgfsTer36. By immunohistochemistry the normal KRT90 protein is expressed in the nail matrix and nail bed in control mice where lesions are located in mutant mice. Immunoreactivity toward equine KRT124, the ortholog of mouse KRT90, is restricted to the nail bed of the hoof and the mouse nail unit. Equine laminitis lesions are similar to those observed in this mutant mouse suggesting that the latter may be a useful model for this horse disease. This first spontaneous mouse mutation affecting the novel Krt90 gene provides new insight into the normal regulation of the molecular pathways of nail development.
2022-07-05 | MSV000089811 | MassIVE
Project description:Nails protect the soft tissue of the tips of digits in humans. In birds and mammals the equivalent claws are used for purposes including capturing prey, digging, climbing, fighting and maintaining dexterity and balance. The molecular mechanism of nail (and claw) development is largely unknown, but we have recently identified a Wnt receptor gene, Frizzled6 (Fzd6), as mutated in a human autosomal-recessive nail dysplasia. To investigate the action of Fzd6 in claw development at the molecular level, we compared gene expression profiles of digit tips of wild-type and Fzd6-/- mice, and show that Fzd6 regulates the transcription of a striking number of epidermal differentiation-related genes. Sixty-three genes encoding keratins, keratin associated proteins, and transglutaminases and their substrates were significantly down-regulated in the knockout mice. Among them, four hard keratins, Krt86, Krt81, Krt34 and Krt31; two epithelial keratins, Krt6a and Krt6b; and transglutaminase1 were known to be expressed in nails and involved in nail abnormality when dysregulated. Immunohistochemical studies revealed decreased expression of Krt86, Krt6b and involucrin in the epidermal portion of the claw field in the knockout embryos. We further show that Dkk4, a Wnt antagonist, was significantly down-regulated in Fzd6-/- mice along with Wnt, Bmp and Hh family genes; and Dkk4 transgenic mice showed a subtly but appreciably modified claw phenotype. Thus, Fzd6-mediated Wnt signaling likely regulates the overall differentiation process of nail/claw formation. Heterozygous Fzd6+/- mice (kindly provided by Dr. J. Nathans) were crossed to generate Fzd6+/-, Fzd6-/- and wild-type offspring. Timed matings were set up to harvest embryos at E14.5, E16.5 and E18.5. The morning after mating was designated as E0.5. Tails and the digital tips from forelimbs of three wild-type and Fzd6-/- mice from each embryonic time-point were excised, immediately frozen on dry ice, and stored at 80 C freezer until use. Genotyping was done as described previously (15). RNA was extracted using Trizol Reagent (Life technologies). RNA from dissected forelimbs from each embryo of the three time-points was used for microarray analysis.
2013-09-13 | E-GEOD-40763 | biostudies-arrayexpress
Project description:We report the genome wide occupancy of p65, H3K4Me3, H3K27Ac and p300 in MCF7-NAIL-WT and MCF7-NAIL-ΔNFκB cells stimulated with TNF alpha for 0min, 45min and 90 min.
2023-09-01 | GSE138308 | GEO
Project description:Cystic Fibrosis Nasal Epithelium Gene Expression by RNAseq
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