Nonmyelinating Schwann Cells Maintain Hematopoietic Stem Cell Hibernation in the Bone Marrow Niche

被引：582

作者：

Yamazaki, Satoshi ^{[1
]}

Ema, Hideo ^{[2
]}

Karlsson, Goran ^{[3
]}

Yamaguchi, Tomoyuki ^{[1
,2
]}

Miyoshi, Hiroyuki ^{[4
]}

Shioda, Seiji ^{[5
]}

Taketo, Makoto M. ^{[4
]}

Karlsson, Stefan ^{[3
]}

Iwama, Atsushi ^{[6
,7
]}

Nakauchi, Hiromitsu ^{[1
,2
]}

机构：

[1] Japan Sci & Technol Agcy, ERATO, Chiyoda Ku, Tokyo 1020075, Japan

[2] Univ Tokyo, Inst Med Sci, Div Stem Cell Therapy, Ctr Stem Cell Biol & Med, Tokyo 1088639, Japan

[3] Univ Lund Hosp, Lund Stem Cell Ctr, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden

[4] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan

[5] Showa Univ, Sch Med, Dept Anat, Shinagawa Ku, Tokyo 1428555, Japan

[6] CREST, Chiyoda Ku, Tokyo 1020075, Japan

[7] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan

来源：

CELL | 2011年 / 147卷 / 05期

关键词：

GROWTH-FACTOR-BETA; TGF-BETA; PERIPHERAL-NERVE; IN-VIVO; ACTIVATION; INTEGRIN; RECEPTOR; PROLIFERATION; MAINTENANCE; QUIESCENCE;

D O I：

10.1016/j.cell.2011.09.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hematopoietic stem cells (HSCs) reside and self-renew in the bone marrow (BM) niche. Overall, the signaling that regulates stem cell dormancy in the HSC niche remains controversial. Here, we demonstrate that TGF-beta type II receptor-deficient HSCs show low-level Smad activation and impaired long-term repopulating activity, underlining the critical role of TGF-beta/Smad signaling in HSC maintenance. TGF-b is produced as a latent form by a variety of cells, so we searched for those that express activator molecules for latent TGF-beta. Nonmyelinating Schwann cells in BM proved responsible for activation. These glial cells ensheathed autonomic nerves, expressed HSC niche factor genes, and were in contact with a substantial proportion of HSCs. Autonomic nerve denervation reduced the number of these active TGF-beta-producing cells and led to rapid loss of HSCs from BM. We propose that glial cells are components of a BM niche and maintain HSC hibernation by regulating activation of latent TGF-beta.

引用

页码：1146 / 1158

页数：13

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