title: Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche.
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.
authors: Japan Science and Technology Agency, ERATO, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Satoshi
authors: S
authors: Yamazaki
authors: Hideo
authors: H
authors: Ema
authors: Göran
authors: G
authors: Karlsson
authors: Tomoyuki
authors: T
authors: Yamaguchi
authors: Hiroyuki
authors: H
authors: Miyoshi
authors: Seiji
authors: S
authors: Shioda
authors: Makoto M
authors: MM
authors: Taketo
authors: Stefan
authors: S
authors: Karlsson
authors: Atsushi
authors: A
authors: Iwama
authors: Hiromitsu
authors: H
authors: Nakauchi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology; D013562:Sympathectomy; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D053782:Transforming Growth Factor beta3