Yamazaki Satoshi, Nakauchi Hiromitsu
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan,
Int J Hematol. 2014 Jun;99(6):695-8. doi: 10.1007/s12185-014-1588-9. Epub 2014 May 10.
Hematopoietic stem cells (HSCs) are clonogenic cells capable of both self-renewal and multilineage differentiation. In adult mouse bone marrow (BM), most HSCs remain in the non-dividing G0-phase of cell cycle, in close contact with supporting cells known as the HSC "niche". In the present study, we focused on signaling mechanisms that regulate stem cell dormancy in the BM niche. We show that TGF-β type II receptor deficiency causes reduced phosphorylation of Smad2/3 and impairs long-term repopulating activity in HSCs, suggesting a significant role for TGF-β/Smad signaling in hematopoiesis. Furthermore, we aimed at defining the candidate BM niche responsible for homeostasis of hematopoiesis, and revealed that non-myelinating Schwann cells sustain HSC hibernation by converting TGF-β from its latent to its active form.
造血干细胞（HSCs）是具有自我更新和多谱系分化能力的克隆形成细胞。在成年小鼠骨髓（BM）中，大多数造血干细胞处于细胞周期的非分裂G0期，与被称为造血干细胞“生态位”的支持细胞紧密接触。在本研究中，我们聚焦于调节骨髓生态位中干细胞休眠的信号传导机制。我们发现，II型转化生长因子-β（TGF-β）受体缺陷会导致Smad2/3磷酸化减少，并损害造血干细胞的长期重建活性，这表明TGF-β/Smad信号在造血过程中具有重要作用。此外，我们旨在确定负责造血稳态的候选骨髓生态位，并发现非髓鞘形成雪旺细胞通过将TGF-β从其潜伏形式转化为活性形式来维持造血干细胞的休眠。
