The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem-cell-niche function
- Centro Nacional de Investigaciones Cardiovasculares, Spain
Abstract
Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. Here we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin- MSCs participate in fetal skeletogenesis, and lose MSC activity soon after birth. In contrast, quiescent neural-crest-derived nestin+ cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC-niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ PDGFRα- cell population also contains Schwann-cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC-niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.
Article and author information
Author details
Reviewing Editor
- Giulio Cossu, University of Manchester, United Kingdom
Ethics
Animal experimentation: Experimental procedures were approved by the Animal Care and Use Committees of the Spanish National Cardiovascular Research Center and Comunidad Autónoma de Madrid (PA-47/11 and ES280790000176)
Version history
- Received: June 16, 2014
- Accepted: September 24, 2014
- Accepted Manuscript published: September 25, 2014 (version 1)
- Version of Record published: October 20, 2014 (version 2)
Copyright
© 2014, Isern et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem-cell-niche function
eLife 3:e03696.
https://doi.org/10.7554/eLife.03696
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