The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.
The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.
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DOI：
10.7554/elife.03696
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发表时间：
2014-09-25
期刊：
影响因子：
7.7
通讯作者：
Méndez-Ferrer S
中科院分区：
文献类型：
--
作者：
Isern J;García-García A;Martín AM;Arranz L;Martín-Pérez D;Torroja C;Sánchez-Cabo F;Méndez-Ferrer S
间充质干细胞（MSC）和骨谱系细胞有助于长骨骨髓中的造血干细胞（HSC）龛。然而，它们的发展关系仍不清楚。在这项研究中，我们证明了不同的MSC群体在发育中的长骨骨髓有不同的功能。再生中胚层来源的巢蛋白-MSC参与胎儿骨骼发育，出生后不久就失去MSC活性。相反，静止的神经嵴来源的巢蛋白+细胞保留MSC活性，但不产生胎儿软骨细胞。相反，它们分化成HSC龛形成MSC，通过分泌Cxcl 12帮助建立HSC龛。这些细胞向骨髓的神经周迁移需要ErbB 3受体。新生的Nestin-GFP+ Pdgfrα−细胞群也含有许旺细胞前体，但不包含成熟的许旺细胞。因此，在发育中的骨髓中，HSC龛形成MSC与交感神经外周神经元和神经胶质细胞具有共同的起源，并且个体发育不同的MSC在软骨内发生和HSC龛形成中具有不重叠的功能。http://dx.doi.org/10.7554/eLife.03696.001在胚胎发育的最初阶段，胚胎是由一群干细胞形成的，这些干细胞可以发育成身体中所有不同类型的组织，从骨骼到脑组织。在以后的生活中，在各种组织中发现了少量的成体干细胞，并提供了一个新细胞库，可用于替换旧的或受损的细胞。造血干细胞最重要的来源是骨髓，它产生和储存能够发育成血液和免疫系统细胞的细胞。这些过程由称为基质细胞的不同骨髓细胞辅助，基质细胞创造了一个专门的局部环境或“生态位”。但是，形成骨骼的基质干细胞是否与发育过程中形成这个小生境的基质干细胞相同呢？或者不同类型的基质干细胞是从胚胎中不同的细胞群发育而来的？此外，目前还不清楚哪些细胞引导血液干细胞朝向形成骨骼。其他类型的细胞，包括神经系统的一些细胞，可以与成人骨髓中的干细胞交流并影响它们的行为。这使得科学家们想知道骨髓龛中的干细胞和与它们交流的细胞是否是从同一类型的胚胎干细胞发展而来的。Isern等人通过检查来自未出生和婴儿小鼠的长骨（例如，腿骨）的骨髓来追踪不同类型的骨髓基质干细胞的发育起源。事实证明，并非所有发育中的骨髓基质干细胞都是一样的。事实上，一个基质干细胞池形成骨骼，并在此过程中失去干细胞活性。相比之下，不同的基质干细胞群从产生神经系统细胞的同一组胚胎细胞发育而来。第二组中的基质干细胞起着小生境的作用，以招募和储存进入的血液干细胞，并在整个生命过程中保持其干细胞活性。Isern等人的发现有助于解释为什么神经系统能够与成人骨髓中的干细胞进行交流，并为理解含有神经组织的器官中的干细胞龛是如何建立的提供了一个模型。DOI：http://dx.doi.org/10.7554/eLife.03696.002网站
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. DOI: http://dx.doi.org/10.7554/eLife.03696.001 During the earliest phases of development, the embryo is formed by groups of stem cells that can develop into all the different types of tissue in the body—from bones to brain tissue. Later in life, small stockpiles of adult stem cells are found in various tissues and provide a reservoir of new cells available for replacing old or damaged cells. The most important source of blood stem cells is the bone marrow, which produces and stores cells that are capable of developing into blood and immune system cells. These processes are assisted by different bone marrow cells called stromal cells, which create a specialized local environment or ‘niche’. But are the stromal stem cells that form the skeleton the same ones that form this niche during development? Or do the various types of stromal stem cells develop from distinct groups of cells in the embryo? Furthermore, it is unclear which cells guide blood stem cells towards the forming bones. Other types of cells, including some of the cells of the nervous system, can communicate with the stem cells in the adult marrow and influence their behavior. This led scientists to wonder whether the stem cells in the bone marrow niche and the cells that communicate with them developed from the same type of embryonic stem cell. Isern et al. tracked down the developmental origins of different types of bone marrow stromal stem cells by examining the bone marrow from the long bones (for example, the bones in the leg) of unborn and infant mice. It turns out that not all stromal stem cells in the developing bone marrow are alike. In fact, one pool of stromal stem cells forms the skeleton and loses stem cell activity in the process. In contrast, a different population of stromal stem cells develops from the same group of embryonic cells that gives rise to the cells of the nervous system. The stromal stem cells in this second group function as a niche to recruit and store the incoming blood stem cells and retain their stem cell activity throughout life. The findings of Isern et al. help to explain why the nervous system is able to communicate with stem cells in the adult marrow, and provide a model for understanding how stem cell niches in organs that contain nerve tissue are established. DOI: http://dx.doi.org/10.7554/eLife.03696.002