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

Yamazaki, Satoshi; Ema, Hideo; Karlsson, Göran LU ; Yamaguchi, Tomoyuki; Miyoshi, Hiroyuki; Shioda, Seiji; Taketo, Makoto M.; Karlsson, Stefan LU ; Iwama, Atsushi and Nakauchi, Hiromitsu (2011) In Cell 147(5). p.1146-1158
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-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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell
volume
147
issue
5
pages
1146 - 1158
publisher
Cell Press
external identifiers
  • wos:000297376600024
  • scopus:81855183667
ISSN
1097-4172
DOI
10.1016/j.cell.2011.09.053
language
English
LU publication?
yes
id
0905f534-9d37-46af-842f-4fb3889d0e77 (old id 2272183)
date added to LUP
2012-01-02 09:49:01
date last changed
2017-11-12 03:11:51
@article{0905f534-9d37-46af-842f-4fb3889d0e77,
  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-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.},
  author       = {Yamazaki, Satoshi and Ema, Hideo and Karlsson, Göran and Yamaguchi, Tomoyuki and Miyoshi, Hiroyuki and Shioda, Seiji and Taketo, Makoto M. and Karlsson, Stefan and Iwama, Atsushi and Nakauchi, Hiromitsu},
  issn         = {1097-4172},
  language     = {eng},
  number       = {5},
  pages        = {1146--1158},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Nonmyelinating Schwann Cells Maintain Hematopoietic Stem Cell Hibernation in the Bone Marrow Niche},
  url          = {http://dx.doi.org/10.1016/j.cell.2011.09.053},
  volume       = {147},
  year         = {2011},
}