TGF-β signaling–deficient hematopoietic stem cells have normal self-renewal and regenerative ability in vivo despite increased proliferative capacity in vitro

The role of Smad signaling in hematopoiesis

“…By mating the animals to the inducible MxCre transgenic mice, the consequences of disrupted TGF-b signaling could be studied in adult hematopoiesis. As expected, since both TbRI and TbRII are believed to be necessary for TGF-b signal transduction, knockout induction of either TbRI or TbRII caused a complete block in TGF-b signaling and the phenotypes in these mice were indistinguishable (Leveen et al, 2002;Larsson et al, 2003). The induction of receptor-knockout in adult mice lead to a lethal disorder by 8-10 weeks after induction, in many ways similar to the phenotype in TGF-b1-deficient mice (Leveen et al, 2002).…”

Cell cycle regulation in hematopoietic stem cells

“…TGF- also directly induces expression of p57 Kip2 , and prevents sequestration of cyclin D1 (Yamazaki et al, 2009;Scandura et al, 2004). Taken together, these results explain a mechanism by which TGF- may enforce HSC quiescence, although the relationship between TGF- and HSC quiescence has not been directly addressed in vivo due to the confounding effect of an autoimmune condition present in mice lacking TGF- signaling components (Larsson et al, 2003). These data may also help explain why SCF and TPO are associated with HSC quiescence and not proliferation in vivo, as factors such as TGF- that are present in the BM niche may prevent activation of Akt by these cytokines.…”

Mechanisms of self-renewal in hematopoietic stem cells

“…Larsson et al found that using a conditional knockout strategy, TGF-β receptor 1-deficient HSCs exhibited a normal cell cycle and long-term repopulating capacity [61]. However, TGF-β receptor 2 deficiency showed reduced repopulating activity [37].…”