In Vivo Human Somitogenesis Guides Somite Development from hPSCs

Haibin Xi; Wakana Fujiwara; Karen Gonzalez; Majib Jan; Simone Liebscher; Ben Van Handel; Katja Schenke-Layland; April D Pyle

doi:10.1016/j.celrep.2017.01.040

In Vivo Human Somitogenesis Guides Somite Development from hPSCs

Cell Rep. 2017 Feb 7;18(6):1573-1585. doi: 10.1016/j.celrep.2017.01.040.

Authors

Haibin Xi¹, Wakana Fujiwara², Karen Gonzalez³, Majib Jan⁴, Simone Liebscher⁵, Ben Van Handel⁶, Katja Schenke-Layland⁷, April D Pyle⁸

Affiliations

¹ 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.
² Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ 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.
⁶ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; CarthroniX Inc., Tarzana, CA 91356, USA.
⁷ 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.
⁸ 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.

Abstract

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.

Keywords: chondrogenesis; development; differentiation; human pluripotent stem cells; osteogenesis; skeletal myogenesis; somite.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Body Patterning / physiology
Cell Differentiation / physiology
Cells, Cultured
Embryonic Development / physiology*
Gene Expression Regulation, Developmental / physiology
Humans
Mesoderm / metabolism
Mesoderm / physiology
Morphogenesis / physiology*
Muscle, Skeletal / metabolism
Muscle, Skeletal / physiology
Pluripotent Stem Cells / metabolism
Pluripotent Stem Cells / physiology*
Signal Transduction / physiology
Somites / metabolism
Somites / physiology*
Transforming Growth Factor beta / metabolism
beta Catenin / metabolism

Substances

Transforming Growth Factor beta
beta Catenin

Abstract

Publication types

MeSH terms

Substances

Grants and funding