Hair follicle stem cell cultures reveal self-organizing plasticity of stem cells and theirprogeny
Hair follicle stem cell cultures reveal self-organizing plasticity of stem cells and theirprogeny
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DOI：
10.15252/embj.201694902
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发表时间：
2017-01-01
期刊：
影响因子：
11.4
通讯作者：
Wickstroem, Sara A.
中科院分区：
文献类型：
--
作者：
Chacon-Martinez, Carlos Andres;Klose, Markus;Wickstroem, Sara A.
了解复杂组织如何通过局部生长、分化和重塑形成、维持和再生，需要了解单细胞行为如何在群体水平上协调。自我更新的毛囊，由一个独特的干细胞群维持，代表了一个很好的范例来解决这个问题。毛囊干细胞（HFSC）调控机制的理解的一个主要障碍是缺乏一个培养系统，概括HFSC的行为，同时允许他们精确的监测和操纵。在这里，我们建立了一个体外培养系统的基础上的3D细胞外基质环境和定义的可溶性因子，这是第一次允许在不存在异源细胞类型的情况下，小鼠多能HFSCs的扩增和长期维持。引人注目的是，该方案促进从头生成HFSC从非HFSC，反之亦然，在一个动态的自组织过程。HFSC及其后代的这种双向互变驱动系统进入群体平衡状态。我们的研究揭示了细胞表型可塑性驱动小生境内群体水平稳态的调控动力学，并为成体干细胞命运的研究提供了发现工具。
Understanding how complex tissues are formed, maintained, and regenerated through local growth, differentiation, and remodeling requires knowledge on how single-cell behaviors are coordinated on the population level. The self-renewing hair follicle, maintained by a distinct stem cell population, represents an excellent paradigm to address this question. A major obstacle in mechanistic understanding of hair follicle stem cell (HFSC) regulation has been the lack of a culture system that recapitulates HFSC behavior while allowing their precise monitoring and manipulation. Here, we establish an invitro culture system based on a 3D extracellular matrix environment and defined soluble factors, which for the first time allows expansion and long-term maintenance of murine multipotent HFSCs in the absence of heterologous cell types. Strikingly, this scheme promotes de novo generation of HFSCs from non-HFSCs and vice versa in a dynamic self-organizing process. This bidirectional interconversion of HFSCs and their progeny drives the system into a population equilibrium state. Our study uncovers regulatory dynamics by which phenotypic plasticity of cells drives population-level homeostasis within a niche, and provides a discovery tool for studies on adult stem cell fate.