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To reflect the developmental process of the human skeleton, hPSC differentiation methods should include osteogenic progenitors (OPs) arising from three distinct embryonic lineages: the paraxial mesoderm, lateral plate mesoderm, and neural crest. Although OP differentiation protocols have been developed, the lineage from which they are derived, as well as characterization of their genetic and molecular differences, has not been well reported. Therefore, to generate lineage-specific OPs from human embryonic stem cells and human induced pluripotent stem cells, we employed stepwise differentiation of paraxial mesoderm-like cells, lateral plate mesoderm-like cells, and neural crest-like cells toward their respective OP subpopulation. Successful differentiation, confirmed through gene expression and in vivo assays, permitted the identification of transcriptomic signatures of all three cell populations. We also report, for the first time, high FGF1 levels in neural crest-derived OPs\u2014a notable finding given the critical role of fibroblast growth factors (FGFs) in osteogenesis and mineral homeostasis. Our results indicate that FGF1 influences RUNX2 levels, with concomitant changes in ERK1\/2 signaling. Overall, our study further validates hPSCs' power to model bone development and disease and reveals new, potentially important pathways influencing these processes.<\/jats:p>\n                  <jats:sec>\n                    <jats:title\/>\n                  <\/jats:sec>","DOI":"10.1002\/stem.3206","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T14:33:07Z","timestamp":1590157987000},"page":"1107-1123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Lineage-specific differentiation of osteogenic progenitors from pluripotent stem cells reveals the FGF1-RUNX2 association in neural crest-derived osteoprogenitors"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-8404","authenticated-orcid":false,"given":"Fahad","family":"Kidwai","sequence":"first","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron W. H.","family":"Mui","sequence":"additional","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Arora","sequence":"additional","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"},{"name":"2 Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kulsum","family":"Iqbal","sequence":"additional","affiliation":[{"name":"3 Department of Health and Human Services, Dental Consult Services, National Institute of Health Dental Clinic, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Hockaday","sequence":"additional","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Fernandez","family":"Castro Diaz","sequence":"additional","affiliation":[{"name":"4 Department of Health and Human Services, Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Cherman","sequence":"additional","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Martin","sequence":"additional","affiliation":[{"name":"5 Department of Health and Human Services, Genomics and Computational Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamsee D.","family":"Myneni","sequence":"additional","affiliation":[{"name":"6 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch\/Adult Stem Cell Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"7 Department of Health and Human Services, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Futrega","sequence":"additional","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sania","family":"Ali","sequence":"additional","affiliation":[{"name":"8 Biology of Global Health, Department of Biology, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall K.","family":"Merling","sequence":"additional","affiliation":[{"name":"1 Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, 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