biostudies-literatureXi HUCLA Center for Duchenne Muscular Dystrophy (CDMD)NCATS NIH HHSRose Hills Foundation Research AwardUCLA Clinical and Translational Science Institute (CTSI)NIH/NIAMSBSCRCNIAMS NIH HHSNIGMS NIH HHSUCLA Muscular Dystrophy P30 Core Center1573-1585https://www.ebi.ac.uk/biostudies/studies/S-EPMC5327729biostudies-literatureUnknown18(6)Somites form during embryonic development and give rise to unique cell and tissue types, such as skeletal muscles and bones and cartilage of the vertebrae. Using somitogenesis-stage human embryos, we performed transcriptomic profiling of human presomitic mesoderm as well as nascent and developed somites. In addition to conserved pathways such as WNT-β-catenin, we also identified BMP and transforming growth factor β (TGF-β) signaling as major regulators unique to human somitogenesis. This information enabled us to develop an efficient protocol to derive somite cells in vitro from human pluripotent stem cells (hPSCs). Importantly, the in-vitro-differentiating cells progressively expressed markers of the distinct developmental stages that are known to occur during in vivo somitogenesis. Furthermore, when subjected to lineage-specific differentiation conditions, the hPSC-derived somite cells were multipotent in generating somite derivatives, including skeletal myocytes, osteocytes, and chondrocytes. This work improves our understanding of human somitogenesis and may enhance our ability to treat diseases affecting somite derivatives.Cell reportsIn Vivo Human Somitogenesis Guides Somite Development from hPSCs.PMC5327729UL1TR000124R01 AR064327UL1 TR000124T34 GM008563R01AR064327P30AR057230P30 AR057230Xi HLiebscher SSchenke-Layland KGonzalez KJan MPyle ADFujiwara WVan Handel BfalseIn Vivo Human Somitogenesis Guides Somite Development from hPSCs.Somites form during embryonic development and give rise to unique cell and tissue types, such as skeletal muscles and bones and cartilage of the vertebrae. Using somitogenesis-stage human embryos, we performed transcriptomic profiling of human presomitic mesoderm as well as nascent and developed somites. In addition to conserved pathways such as WNT-β-catenin, we also identified BMP and transforming growth factor β (TGF-β) signaling as major regulators unique to human somitogenesis. This information enabled us to develop an efficient protocol to derive somite cells in vitro from human pluripotent stem cells (hPSCs). Importantly, the in-vitro-differentiating cells progressively expressed markers of the distinct developmental stages that are known to occur during in vivo somitogenesis. Furthermore, when subjected to lineage-specific differentiation conditions, the hPSC-derived somite cells were multipotent in generating somite derivatives, including skeletal myocytes, osteocytes, and chondrocytes. This work improves our understanding of human somitogenesis and may enhance our ability to treat diseases affecting somite derivatives.2017-01-01T00:00:00Z2017 Feb2024-11-20T23:24:28.187Z2019-03-27T02:37:27ZS-EPMC53277292817853110.1016/j.celrep.2017.01.040