Is TGF-β a stemness regulator?
Stefan Karlsson LUND UNIVERSITY In this issue of Blood, Yamazaki and colleagues show that TGF-β inhibits cytokine-mediated LRC clustering in purified HSCs freshly isolated from the bone marrow and induces hibernation of HSCs ex vivo. Since cytokine stimulation of LRC is important to stimulate proliferation of HSCs, the authors propose that TGF-β may be a hibernation/quiescence regulator in the HSC bone marrow niche. It has been 2 decades now since Ruscetti and colleagues discovered TGF-β as the first potent negative regulator of hematopoietic stem- and progenitor cells.1 Through many detailed experiments, it was demonstrated that TGF-β treatment of hematopoietic stem and progenitor cells inhibited their proliferation in vitro (with the exception CFU-GM progenitors). From these initial studies it was not clear whether TGF-β is a physiologic regulator of hematopoietic stem cells (HSCs) in vivo. Once conditional knockout mice were available to study the role of TGF-β signaling in the regu
