Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells

Denis Evseenko(University of California, Los Angeles), Yuhua Zhu(University of California, Los Angeles), Katja Schenke‐Layland(University of California, Los Angeles), Jeffrey Kuo(University of California, Los Angeles), Brooke Latour(University of California, Los Angeles), Shundi Ge(University of California, Los Angeles), Jessica Scholes(University of California, Los Angeles), Gautam Dravid(University of California, Los Angeles), Xinmin Li(University of California, Los Angeles), W. Robb MacLellan(University of California, Los Angeles), Gay M. Crooks
Proceedings of the National Academy of Sciences
July 19, 2010
10.1073/pnas.1002077107
Cited by 266Open Access
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Abstract

Our understanding of how mesodermal tissue is formed has been limited by the absence of specific and reliable markers of early mesoderm commitment. We report that mesoderm commitment from human embryonic stem cells (hESCs) is initiated by epithelial-to-mesenchymal transition (EMT) as shown by gene expression profiling and by reciprocal changes in expression of the cell surface proteins, EpCAM/CD326 and NCAM/CD56. Molecular and functional assays reveal that the earliest CD326-CD56+ cells, generated from hESCs in the presence of activin A, BMP4, VEGF, and FGF2, represent a multipotent mesoderm-committed progenitor population. CD326-CD56+ progenitors are unique in their ability to generate all mesodermal lineages including hematopoietic, endothelial, mesenchymal (bone, cartilage, fat, fibroblast), smooth muscle, and cardiomyocytes, while lacking the pluripotency of hESCs. CD326-CD56+ cells are the precursors of previously reported, more lineage-restricted mesodermal progenitors. These findings present a unique approach to study how germ layer specification is regulated and offer a promising target for tissue engineering.

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