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Cell. 2011 Nov 23;147(5):1146-58. doi: 10.1016/j.cell.2011.09.053.

Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche.

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  • 1Japan Science and Technology Agency, ERATO, Chiyoda-ku, Tokyo 102-0075, Japan.

Abstract

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-β type II receptor-deficient HSCs show low-level Smad activation and impaired long-term repopulating activity, underlining the critical role of TGF-β/Smad signaling in HSC maintenance. TGF-β is produced as a latent form by a variety of cells, so we searched for those that express activator molecules for latent TGF-β. 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-β-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-β.

Copyright © 2011 Elsevier Inc. All rights reserved.

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PMID:
22118468
[PubMed - indexed for MEDLINE]
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