Figure 4.

Transforming growth factor β (TGF-β) family signaling in hematopoietic stem cells. The niche provides signaling support to maintain hematopoietic stem-cell (HSC) state. CXCL12 and stem-cell factor (SCF) are both required for HSC maintenance and are provided by mesenchymal stem cells (MSCs) and endothelial cells. Inactive (latent) TGF-β is produce by HSCs and other cells in the niche. Nonmyelinating Schwann cells express integrin αvβ8, which binds the latent TGF-β complex and recruits metalloproteinases that cleave latent TGF-β and release active TGF-β. TGF-β acts through TβRII on the surface of HCSs to inhibit proliferation and promote maintenance of HSC state.