Regulation of embryonic stem cell self-renewal and differentiation by TGF-β family signaling
- 130 Downloads
Embryonic stem (ES) cells are characterized by their ability to indefinitely self-renew and potential to differentiate into all the cell lineages of the body. ES cells are considered to have potential applications in regenerative medicine. In particular, the emergence of an ES cell analogue — induced pluripotent stem (iPS) cells via somatic cell reprogramming by co-expressing a limited number of critical stemness-related transcriptional factors has solved the problem of obtaining patient-specific pluripotent cells, encouraging researchers to develop more specific and functional cell lineages from ES or iPS cells for broad therapeutic applications. ES cell fate choice is delicately controlled by a core transcriptional network, epigenetic modification profiles and complex signaling cascades both intrinsically and extrinsically. Of these signals, transforming growth factor β (TGF-β) family members, including TGF-β, bone morphogenetic protein (BMP), Activin and Nodal, have been reported to influence cell self-renewal and a broad spectrum of lineage differentiation in ES cells, in accordance with the key roles of TGF-β family signaling in early embryo development. In this review, the roles of TGF-β family signals in coordinating ES cell fate determination are summarized.
Keywordsembryonic stem cell TGF-β BMP Activin Nodal self-renewal differentiation
Unable to display preview. Download preview PDF.
- 17.Xiao L, Yuan X, Sharkis S J. Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells. Stem Cells, 2006, 24:1476–1486 10.1634/stemcells.2005-0299, 1:CAS:528:DC%2BD28XhtFKlsbbM, 16456129PubMedCrossRefGoogle Scholar
- 19.Wu Z, Zhang W, Chen G, et al. Combinatorial signals of activin/nodal and bone morphogenic protein regulate the early lineage segregation of human embryonic stem cells. J Biol Chem, 2008, 283:24991–25002 10.1074/jbc.M803893200, 1:CAS:528:DC%2BD1cXhtVGktbnF, 18596037PubMedPubMedCentralCrossRefGoogle Scholar
- 32.Park C, Afrikanova I, Chung Y S, et al. A hierarchical order of factors in the generation of FLK1- and SCL-expressing hematopoietic and endothelial progenitors from embryonic stem cells. Development, 2004, 131:2749–2762 10.1242/dev.01130, 1:CAS:528:DC%2BD2cXltlajt7s%3D, 15148304PubMedCrossRefGoogle Scholar
- 39.Takei S, Ichikawa H, Johkura K, et al. Bone morphogenetic protein-4 promotes induction of cardiomyocytes from human embryonic stem cells in serum-based embryoid body development. Am J Physiol Heart Circ Physiol, 2009, 296:H1793–1803 10.1152/ajpheart.01288.2008, 1:CAS:528:DC%2BD1MXnsF2ltrk%3D, 19363129PubMedCrossRefGoogle Scholar
- 42.Pisconti A, Brunelli S, Di Padova M, et al. Follistatin induction by nitric oxide through cyclic GMP: A tightly regulated signaling pathway that controls myoblast fusion. J Cell Biol, 2006, 172:233–244 10.1083/jcb.200507083, 1:CAS:528:DC%2BD28XntV2isw%3D%3D, 16401724PubMedPubMedCentralCrossRefGoogle Scholar
- 49.Hajare M, Delphine C, Youssef H, et al. Osteogenic differentiation of ES cell-derived EBs mediated by embedded BMP-2 and TGF-beta-1 in a polyelectrolyte multilayer film. In: M. Firestone J S, N. Malmstadt eds. Mater Res Soc Symp Proc 950E. Warrendale, PA, 2007:0950-D0910-0904Google Scholar