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

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Author

  • Satoshi Yamazaki
  • Hideo Ema
  • Göran Karlsson
  • Tomoyuki Yamaguchi
  • Hiroyuki Miyoshi
  • Seiji Shioda
  • Makoto M. Taketo
  • Stefan Karlsson
  • Atsushi Iwama
  • Hiromitsu Nakauchi

Summary, in English

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.

Publishing year

2011

Language

English

Pages

1146-1158

Publication/Series

Cell

Volume

147

Issue

5

Document type

Journal article

Publisher

Cell Press

Topic

  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1097-4172