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BMP4 initiates human embryonic stem cell differentiation to trophoblast
Author(s): Xu RH, Chen X, Li DS, Li R, Addicks GC, Glennon C, Zwaka TP, Thomson JA
Source: NATURE BIOTECHNOLOGY    Volume: 20    Issue: 12    Pages: 1261-1264    Published: DEC 2002  
Times Cited: 263     References: 33     
Abstract: The excitement and controversy surrounding the potential role of human embryonic stem (ES)(1,2) cells in transplantation therapy have often overshadowed their potentially more important use as a basic research tool for understanding the development and function of human tissues. Human ES cells can proliferate without a known limit and can form advanced derivatives of all three embryonic germ layers. What is less widely appreciated is that human ES cells can also form the extra-embryonic tissues that differentiate from the embryo before gastrulation. The use of human ES cells to derive early human trophoblast is particularly valuable, because it is difficult to obtain from other sources and is significantly different from mouse trophoblast. Here we show that bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor-beta (TGF-beta) superfamily, induces the differentiation of human ES cells to trophoblast. DNA microarray, RT-PCR, and immunoassay analyses demonstrate that the differentiated cells express a range of trophoblast markers and secrete placental hormones. When plated at low density, the BMP4-treated cells form syncytia that express chorionic gonadotrophin (CG). These results underscore fundamental differences between human and mouse ES cells, which differentiate poorly, if at all, to trophoblast(3). Human ES cells thus provide a tool for studying the differentiation and function of early human trophoblast and could provide a new understanding of some of the earliest differentiation events of human postimplantation development.
Document Type: Article
Language: English
Reprint Address: Thomson, JA (reprint author), Univ Wisconsin, Natl Primate Res Ctr, Madison, WI 53715 USA
Addresses:
1. Univ Wisconsin, Natl Primate Res Ctr, Madison, WI 53715 USA
2. Univ Wisconsin, Sch Med, Dept Anat, Madison, WI 53715 USA
3. WiCell Res Inst, Madison, WI 53715 USA
4. Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA
Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA
Subject Category: Biotechnology & Applied Microbiology
IDS Number: 620VF
ISSN: 1087-0156
DOI: 10.1038/nbt761
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