Bone marrow Schwann cells induce hematopoietic stem cell hibernation
Bone marrow Schwann cells induce hematopoietic stem cell hibernation
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骨髓雪旺细胞诱导造血干细胞冬眠
DOI：
10.1007/s12185-014-1588-9
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发表时间：
2014
影响因子：
2.1
通讯作者：
Nakauchi H
中科院分区：
文献类型：
--
作者：
Yamazaki S;Nakauchi H
造血干细胞（Hematopoietic stem cells，HSCs）是一类具有自我更新和多向分化能力的克隆细胞。在成年小鼠骨髓（BM）中，大多数HSC保持在细胞周期的非分裂G 0期，与称为HSC“龛”的支持细胞紧密接触。在本研究中，我们专注于调节BM生态位中干细胞休眠的信号传导机制。我们发现，TGF-β II型受体缺陷导致Smad 2/3磷酸化减少，并损害HSC的长期再生活性，表明TGF-β/Smad信号在造血中的重要作用。此外，我们旨在确定负责造血稳态的候选BM生态位，并揭示非髓鞘化雪旺细胞通过将TGF-β从其潜伏形式转化为其活性形式来维持HSC冬眠。
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.