Roles of TGF-β family signaling in stem cell renewal and differentiation

Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells

“…Activin/Nodal signaling has been established as a pivotal regulatory cue to instruct ES cell fate determination [5][6][7], however, the underlying molecular basis is not fully understood. In this study, we found that Smad2-dependent Activin/Nodal signaling is dispensable for mouse ES cell self-renewal maintenance but required for various lineage differentiation, especially toward the mesendoderm direction.…”

“…A recent report also suggested that endogenous Nodal signaling indirectly modulates pluripotency via negative regulation of BMP signaling [24]. When ES cells are induced to differentiate, both branches of the TGF-β family signals are implicated in various lineage commitment, serving as either inducers or repressors in a contextdependent manner [5][6][7]. However, the exact role of the Smad-mediated Activin/Nodal signaling in self-renewal and differentiation is still largely unclear.…”

“…Among those signals, members of the transforming growth factor-β (TGF-β) superfamily were recognized as the crucial ones for both mouse and human ES cell fate choices and were representative to show the distinct requirements of the two species [5][6][7]. The TGF-β superfamily comprises two main groups: the TGF-β/Activin/ Nodal group and the bone morphogenetic protein (BMP)/ growth and differentiation factor (GDF) group.…”

p21-activated Kinase 2 (PAK2) Inhibits TGF-β Signaling in Madin-Darby Canine Kidney (MDCK) Epithelial Cells by Interfering with the Receptor-Smad Interaction

“…Transforming growth factor-␤ (TGF-␤) 4 is a pleiotropic cytokine regulating diverse cellular processes in a cell type-and context-dependent manner (1)(2)(3)(4)(5). To achieve this, TGF-␤ elicits multiple signaling pathways, and the R-Smads (receptorregulated Smad proteins) (Smad2 and Smad3 for TGF-␤ signaling)-mediated canonical pathway is involved in most of TGF-␤-mediated functions (6 -10).…”

Zinc Finger Protein 451 Is a Novel Smad Corepressor in Transforming Growth Factor-β Signaling

“…Activins, and related proteins (1)(2)(3)(4). Members of the TGF-␤ superfamily control diverse developmental processes and the pathogenesis of many diseases through direct transcriptional regulation (5).…”