期刊
NATURE BIOTECHNOLOGY
卷 30, 期 6, 页码 531-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.2239
关键词
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资金
- California Institute of Regenerative Medicine (CIRM) [RC1-00354-1, RT2-02060]
- Human Frontier Science Organization (HFSPO) [CDA0063/2007-C]
- Stanford Medical Scholars Program
- Human Frontier Science Program (HFSP) Long Term Fellowship
To identify early populations of committed progenitors derived from human embryonic stem cells (hESCs), we screened self-renewing, BMP4-treated and retinoic acid-treated cultures with >400 antibodies recognizing cell-surface antigens. Sorting of >30 subpopulations followed by transcriptional analysis of developmental genes identified four distinct candidate progenitor groups. Subsets detected in self-renewing cultures, including CXCR4(+) cells, expressed primitive endoderm genes. Expression of Cxcr4 in primitive endoderm was confirmed in visceral endoderm of mouse embryos. BMP4-induced progenitors exhibited gene signatures of mesoderm, trophoblast and vascular endothelium, suggesting correspondence to gastrulation-stage primitive streak, chorion and allantois precursors, respectively. Functional studies in vitro and in vivo confirmed that ROR2(+) cells produce mesoderm progeny, APA(+) cells generate syncytiotrophoblasts and CD87(+) cells give rise to vasculature. The same progenitor classes emerged during the differentiation of human induced pluripotent stem cells (hiPSCs). These markers and progenitors provide tools for purifying human tissue-regenerating progenitors and for studying the commitment of pluripotent stem cells to lineage progenitors.
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