In 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.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Haibin
H
Xi
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Wakana
W
Fujiwara
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Karen
K
Gonzalez
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Majib
M
Jan
Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, 72074 Tübingen, Germany; Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology, 70569 Stuttgart, Germany.
Simone
S
Liebscher
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; CarthroniX Inc., Tarzana, CA 91356, USA.
Ben
B
Van Handel
Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, 72074 Tübingen, Germany; Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology, 70569 Stuttgart, Germany; Cardiovascular Research Laboratories, Department of Medicine and Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Katja
K
Schenke-Layland
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: apyle@mednet.ucla.edu.
April D
AD
Pyle
D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008648:Mesoderm / Q000378:metabolism / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019170:Somites / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D016212:Transforming Growth Factor beta; D051176:beta Catenin
chondrogenesis; development; differentiation; human pluripotent stem cells; osteogenesis; skeletal myogenesis; somite