期刊
ELIFE
卷 3, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.03696
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资金
- Spanish Ministry of Economy and Competitiveness through the Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III [SB2010-0023]
- Plan Nacional grants [BFU2012-35892, SAF-2011-30308]
- Ramon y Cajal Program [RYC-2011-09209, RYC-2009-04703]
- Marie Curie Career Integration Program [FP7-PEOPLE-2011-RG-294262]
- ConSEPOC-Comunidad de Madrid [S2010/BMD-2542]
- Spanish Network of Cell Therapy (TerCel)
- Fundacion Ramon Areces
- Fundacion La Caixa
- International Early Career Scientist grant from the Howard Hughes Medical Institute
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 in the same bones 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(+) PDGFR alpha(-) 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.
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