Elife. 2014 Sep 25;3. doi: 10.7554/eLife.03696. [Epub ahead of print]

The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem-cell-niche function.

Isern J¹, García-García A¹, Martín AM¹, Arranz L¹, Martín-Pérez D¹, Torroja C¹, Sánchez-Cabo F¹, Méndez-Ferrer S².

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.