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

被引：196

作者：

Evseenko, Denis ^{[1
,2
]}

Zhu, Yuhua ^{[1
,2
]}

Schenke-Layland, Katja ^{[3
]}

Kuo, Jeffrey ^{[1
,2
]}

Latour, Brooke ^{[1
,2
]}

Ge, Shundi ^{[1
,2
]}

Scholes, Jessica ^{[1
,2
]}

Dravid, Gautam ^{[1
,2
]}

Li, Xinmin ^{[1
,2
]}

MacLellan, W. Robb ^{[3
]}

Crooks, Gay M. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Broad Stem Cell Res Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Cardiovasc Res Lab, David Geffen Sch Med, Los Angeles, CA 90095 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 31期

关键词：

CD326; CD56; epithelial-to-mesenchymal transition; mesenchyme; hematopoiesis; CARDIOVASCULAR PROGENITOR CELLS; ADHESION MOLECULE; MOUSE; MAINTENANCE; PRECURSORS; PHENOTYPE; MARKER; SOX17;

D O I：

10.1073/pnas.1002077107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：13742 / 13747

页数：6

共 24 条

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