GPMDB00247OtherHaas S, et al.InstrumentNot AvailableNot availableMus_musculus_viruses, 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Institute for Stem Cell Technology and Experimental Medicine, et al.CL:0000037 hematopoietic stem cellGPMDBInfections are associated with extensive platelet consumption, representing a high risk for health. However, the mechanism coordinating the rapid regeneration of the platelet pool during such stress conditions remains unclear. Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults. During homeostasis, SL-MkPs are maintained in a primed but quiescent state, thus contributing little to steady-state megakaryopoiesis. Even though lineage-specific megakaryocyte transcripts are expressed, protein synthesis is suppressed. In response to acute inflammation, SL-MkPs become activated, resulting in megakaryocyte protein production from pre-existing transcripts and a maturation of SL-MkPs and other megakaryocyte progenitors. This results in an efficient replenishment of platelets that are lost during inflammatory insult. Thus, our study reveals an emergency machinery that counteracts life-threatening platelet depletions during acute inflammation.Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors.Haas Simon S,Hansson Jenny J,Klimmeck Daniel D,Loeffler Dirk D,Velten Lars L,Uckelmann Hannah H,Wurzer Stephan S,Prendergast Áine M ÁM,Schnell Alexandra A,Hexel Klaus K,Santarella-Mellwig Rachel R,Blaszkiewicz Sandra S,Kuck Andrea A,Geiger Hartmut H,Milsom Michael D MD,Steinmetz Lars M LM,Schroeder Timm T,Trumpp Andreas A,Krijgsveld Jeroen J,Essers Marieke A G MA,Haas Simon S, Hansson Jenny J, Klimmeck Daniel D, Loeffler Dirk D, Velten Lars L, Uckelmann Hannah H, Wurzer Stephan S, Prendergast Áine M ÁM, Schnell Alexandra A, Hexel Klaus K, Santarella-Mellwig Rachel R, Blaszkiewicz Sandra S, Kuck Andrea A, Geiger Hartmut H, Milsom Michael D MD, Steinmetz Lars M LM, Schroeder Timm T, Trumpp Andreas A, Krijgsveld Jeroen J, Essers Marieke A G MAmegalocaryocyte, hematopoietic precursor cell, blood forming stem cell, hemopoietic progenitor cell, inflammatory response, Inflammations, Megakaryocyte, CFU-S, hematopoietic progenitor cell, Inflammation, blutbildende Stammzelle, hemopoietic stem cell, progenitor cell, megacaryocyte, inflammation, HSC cell, colony forming unit hematopoietic, HSC, Emergency, colony forming unit spleen, megalokaryocyte.hematopoietic precursor cell, School-Age Populations, Populations, data, IFNBR, Megakaryocyte, CFU-S, Infar, Ifar, Ifrc, cell, hemopoietic stem cell, axis, Emergency., megacaryocyte, stem cell, HSC cell, stalk, IFN-alpha-REC, CD118, HSC, Hedgehog signalling complex, Population, Ito cell, School Age Populations, Cell, culm, megalocaryocyte, School-Age, liver stellate cell, blood forming stem cell, Experiment, IFNAR, hemopoietic progenitor cell, hematopoietic progenitor cell, primary axis, blutbildende Stammzelle, IFRC, School Age, progenitor cell, School-Age Population, Ifnar, School Age Population, colony forming unit hematopoietic, primary stem, AVP, megalokaryocyte, colony forming unit spleenmegalocaryocyte, hematopoietic precursor cell, blood forming stem cell, hemopoietic progenitor cell, inflammatory response, Inflammations, Megakaryocyte, CFU-S, hematopoietic progenitor cell, Inflammation, blutbildende Stammzelle, hemopoietic stem cell, progenitor cell, megacaryocyte, inflammation, HSC cell, colony forming unit hematopoietic, HSC, Emergency, colony forming unit spleen, megalokaryocyte.hematopoietic precursor cell, protein translation, CPD photolyase activity, lifespan, Inflammations, PhrB photolyase activity, hemopoietic stem cell, Blood, stalk, Yperite, photoreactivating enzyme activity, pigmented epithelium, deoxyribodipyrimidine photolyase activity, stratum pigmentosum retinae, megalocaryocyte, Relative, School-Age, blood forming stem cell, Thrombocytes, hematopoietic progenitor cell, responsivity, thrombocyte, 1, stratum pigmentosa retinae, outer pigmented layer of retina, 1'-thiobis(2-chloroethane), primary stem, epithelium, Normalities, average, School-Age Populations, reactivity, study, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, inflammatory response, CFU-S, Infections, cell, entire lifespan, entire life cycle, pigmented retina, inflammation, proteins, Population, inhibition of homeostatic process, Estimated, culm, DNA cyclobutane dipyrimidine photolyase activity, Lost, bis(2-chloroethyl) sulphide, liver stellate cell, pigment epithelium of retina, anucleate thrombocyte, Inflammation, blutbildende Stammzelle, 1-chloro-2-[(2-chloroethyl)sulfanyl]ethane, mustard gas, negative regulation of homeostatic process, pigmented retina epithelium, homeostasis, associated, School Age Population, Thrombocyte, InChIKey=QKSKPIVNLNLAAV-UHFFFAOYAK, sulfur mustard, Autoregulation, PRE, protein anabolism, protein biosynthetic process, Megakaryocyte, PLATEST, 1-chloro-2-[(2-chloroethyl)thio]ethane, axis, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, InChI=1/C4H8Cl2S/c5-1-3-7-4-2-6/h1-4H2, Blood Platelet, Normalcy, HSC, Hedgehog signalling complex, pigmented retinal epithelium, Ito cell, ClCCSCCCl, Cell, results, polypeptide, stratum pigmentosum (retina), hemopoietic progenitor cell, bis(2-chloroethyl)sulfane, positive regulation of homeostatic process, retinal pigment, School Age, Relative Risks, deoxyribonucleic photolyase activity, protein formation, dipyrimidine photolyase (photosensitive), protein biosynthesis, colony forming unit hematopoietic, regulation of homeostatic process, retinal pigment layer, Relative Risk, Regenerations, Populations, RPE, Risk, Normality, photolyase activity, retinal pigmented epithelium, life, Risks, megacaryocyte, Senfgas, Inflammation., HSC cell, enucleate thrombocyte, retinal pigment epithelium, School Age Populations, p. pigmentosa retinae, blood platelets, phr A photolyase activity, Health, activation of homeostatic process, DNA-photoreactivating enzyme, primary axis, protein synthesis, progenitor cell, C4H8Cl2S, Platelet, blood platelet, deoxyribonucleate pyrimidine dimer lyase (photosensitive), School-Age Population, response, platelet, megalokaryocyte, Emergency, Platelets, colony forming unit spleen2407http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023393dbgap_ncbi~0patentfamilies~0rfam~0merops~0complex-portal~0uniprot~0wormbaseparasite~0embl-covid19~0reactome~0emdb~0wgs_masters~0ebiweb_resources~0opentargets_genetics~0biomodels_all~0ipd-mhc~0ebiweb_teams~0taxonomy~0genome_assembly~0sc-experiments~0ebiweb_people~0enzymeportal_enzymes~0ipd-nhkir~0cellosaurus~0pdbe~0chebi~0patentproteins~0interpro7~0uniref~0chembl~0pdbekb~0gpcrdb~0hgnc~0sc-genes~0intact~0rhea~0ebiweb_training~0alphafold~0imgt-hla~0patentnucleotides~0ensemblroot~0eva_studies~0non-coding~0europepmc~0pubmed~1identifiers_registry~0pdbechem~0hpa-covid19~0eva-variants-covid19~0biosamples~0gwas_catalog~0biotools~0tls_masters~0mesh~0coding~0sra~1opentargets~0efo~0embl-pathogen~0pride~1human_diseases~0geo_datasets~0embl~0treefam~0project~1uniparc~0ols~0dgva~0intenz~0go~0tsa_masters~0biosamples-covid19~0ebiweb_corporate~0omim~0lrg~0earlycause-molecular-sequences~0ipd-kir~0empiar~0rnacentral~0orcid_data_claims~0gpmdb~2lineage-covid19~0metagenomics~0pfam~0pride archive~1varsite~00Resource Reanalysis0.00.00.0074028377544725481.00.0falseInflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors.Data from ProteomeXchange, PXD ID: PXD001500. Experiment: IFNAR_KO_Prog_78a, file: 120503_JH_IFNAR_KO_Prog_78a_10.mzml. Published as part of Cell Stem Cell. 2015 Aug 19. pii: S1934-5909(15)00306-9 . From the Abstract: {{i}} ... Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults ... {{/i}}2015-08-28GPM3231002339326299573PXD001500PXD001500