Roles of TGF-β family signals in the fate determination of pluripotent stem cells

Semin Cell Dev Biol. 2014 Aug:32:98-106. doi: 10.1016/j.semcdb.2014.05.017. Epub 2014 Jun 6.


Members of the transforming growth factor-β (TGF-β) family have been implicated in embryogenesis as well as in the determination of the cell fates of mouse and human embryonic stem (ES) cells, which are characterized by their self-renewal and pluripotency. The cellular responses to TGF-β family signals are divergent depending on the cellular context and local environment. TGF-β family signals play critical roles both in the maintenance of the pluripotent state of ES cells by inducing the expression of Nanog, Oct4, and Sox2, and in their differentiation into various cell types by regulating the expression of master regulatory genes. Moreover, multiple lines of evidence have suggested the importance of TGF-β family signals in establishing induced pluripotent stem (iPS) cells. Since ES and iPS cells have great potential for applications in regenerative medicine, it is critical to figure out the mechanisms underlying their self-renewal, pluripotency, and differentiation. Here, we discuss the roles of TGF-β family ligands and their downstream signaling molecules, Smad proteins, in the maintenance of the pluripotency and lineage specification of mouse and human ES and iPS cells.

Keywords: BMP; Differentiation; ES cells; Pluripotency; TGF-β; iPS cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Gene Expression
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*


  • Transforming Growth Factor beta