Smad7 promotes self-renewal of hematopoietic stem cells

The role of Smad signaling in hematopoiesis

“…In contrast, BM cells overexpressing Smad7 in a stroma-free ex vivo liquid culture do not exhibit increased proliferative capacity. Rather, the proliferation is reduced (Blank et al, 2004). The findings indicate that a total block in Smad signaling increases selfrenewal of HSC in the BM microenvironment and that signaling crosstalk, perhaps mediated by the cells in the BM HSC niches, will increase self-renewal in Smad signaling-deficient HSC.…”

“…The Smad7 protein is produced in Lin À hematopoietic cells and Smad7 mRNA is expressed in purified LSKCD34 À murine HSC (unpublished observations). When BM cells overexpressing Smad7 are transplanted into irradiated recipients, the repopulation activity is increased, and upon serial transplantation, there is a significant increase in the regeneration of all hematopoietic lineages (Blank et al, 2004). This demonstrates that enforced expression of Smad7 can increase self-renewal of HSC in vivo.…”

A network including TGFβ/Smad4, Gata2, and p57 regulates proliferation of mouse hematopoietic progenitor cells

“…Canonical TGFβ signaling has been shown to control proliferation of HSPCs through Smad proteins 5,6 . To investigate if Gata2 and p57 are regulated via Smad signaling we used Smad4 -/-LSK cells, deficient in all canonical TGFβ signal transduction and 11 resistant to TGFβ-induced growth arrest 6 .…”

“…One of these factors is transforming growth factor-β (TGFβ), an evolutionarily conserved growth factor with a well-documented, potent inhibitory effect on hematopoietic stem and progenitor cell (HSPC) proliferation in vitro [2][3][4] , as well as a role in HSC self-renewal in vivo [5][6][7] .…”

“…Thus, this study represents the first detailed mechanistic insight to TGFβ-induced growth arrest in the context of hematopoietic progenitor cells. 5 …”