| | |  | | | | Record from Web of Science® | | | | | | |
| Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells |
|
|
| Author(s): Xiao L (Xiao, Lei), Yuan X (Yuan, Xuan), Sharkis SJ (Sharkis, Saul J.) |
| Source: STEM CELLS Volume: 24 Issue: 6 Pages: 1476-1486 Published: JUN 2006 |
| Times Cited: 68 References: 45 |
| Abstract: Human embryonic stem cells (hESCs) self-renew indefinitely while maintaining pluripotency. The molecular mechanism underlying hESCs self-renewal and pluripotency is poorly understood. To identify the signaling pathway molecules that maintain the proliferation of hESCs, we performed a microarray analysis comparing an aneuploid H1 hESC line (named H1T) versus euploid H1 hESC line because the H1T hESC line demonstrates a selfrenewal advantage while maintaining pluripotency. We find differential gene expression for the Nodal/Activin, fibroblast growth factor (FGF), Wnt, and Hedgehog (Hh) signaling pathways in the H1T line, which implicates each of these molecules in maintaining the undifferentiated state, whereas the bone morphogenic protein (BMP) and Notch pathways could promote hESCs differentiation. Experimentally, we find that Activin A is necessary and sufficient for the maintenance of self-renewal and pluripotency of hESCs and supports long-term feeder and serum-free growth of hESCs. We show that Activin A induces the expression of Oct4, Nanog, Nodal, Wnt3, basic FGF, and FGF8 and suppresses the BMP signal. Our data indicates Activin A as a key regulator in maintenance of the stemness in hESCs. This finding will help elucidate the complex signaling network that maintains the hESC phenotype and function. |
| Document Type: Article |
| Language: English |
| Reprint Address: Sharkis, SJ (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Room 551,1550 Orleans St, Baltimore, MD 21231 USA |
Addresses:
1. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA |
| Publisher: ALPHAMED PRESS, 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA |
| Subject Category: Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology |
| IDS Number: 085YC |
| ISSN: 1066-5099 |
| DOI: 10.1634/stemcells.2005-0299 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |