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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Bone Marrow / physiology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neuroglia / metabolism
  • Schwann Cells / cytology*
  • Schwann Cells / physiology
  • Sympathectomy
  • Transforming Growth Factor beta3 / metabolism*

Substances

  • Antigens, CD34
  • Transforming Growth Factor beta3