Isern Joan, García-García Andrés, Martín Ana M, Arranz Lorena, Martín-Pérez Daniel, Torroja Carlos, Sánchez-Cabo Fátima, Méndez-Ferrer Simón
Stem Cell Niche Pathophysiology Group, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Elife. 2014 Sep 25;3:e03696. doi: 10.7554/eLife.03696.
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. In this study, 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.
间充质干细胞（MSCs）和成骨谱系细胞对长骨骨髓中的造血干细胞（HSCs）微环境有贡献。然而，它们之间的发育关系仍不清楚。在本研究中，我们证明了长骨发育骨髓中不同的MSC群体具有不同的功能。增殖性中胚层来源的巢蛋白阴性（nestin-）MSCs参与胎儿骨骼生成，并在出生后不久失去MSC活性。相反，静止的神经嵴来源的巢蛋白阳性（nestin+）细胞保留MSC活性，但不产生胎儿软骨细胞。相反，它们分化为形成HSC微环境的MSCs，通过分泌Cxcl12帮助建立HSC微环境。这些细胞向骨髓的神经周迁移需要ErbB3受体。新生的巢蛋白绿色荧光蛋白阳性（Nestin-GFP+）血小板衍生生长因子受体α阴性（Pdgfrα-）细胞群体也包含雪旺细胞前体，但不包含成熟雪旺细胞。因此，在发育中的骨髓HSC微环境形成的MSCs与交感神经外周神经元和神经胶质细胞有共同的起源，并且发育上不同的MSCs在软骨内成骨和HSC微环境形成中具有不重叠的功能。
