Dynamic heterogeneity as a strategy of stem cell self-renewal
Dynamic heterogeneity as a strategy of stem cell self-renewal
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DOI：
10.1073/pnas.1602779113
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发表时间：
2016-07-05
影响因子：
11.1
通讯作者：
Simons, Benjamin D.
中科院分区：
文献类型：
--
作者：
Greulich, Philip;Simons, Benjamin D.
为了维持循环成体组织的稳态，需要精确调节干细胞增殖和分化之间的平衡。为了研究干细胞如何实现完美的自我更新，重点放在干细胞通过单向增殖层次顺序进展的模型上。然而，对组织再生的研究已经揭示了令人惊讶的灵活性程度，通常致力于分化的细胞能够在损伤后恢复干细胞能力。在这里，我们调查是否可逆转移的状态之间的细胞准备增殖或分化可能提供一个可行的机制，即使在正常的生理条件下，异质干细胞群体保持稳态。通过解决克隆动力学，我们表明，这种模型的“动态异质性”可能同样能够描述最近的谱系追踪检测涉及上皮组织的结果。此外，与有限的小生境进入的竞争一起，这样的模型可以提供使组织稳态稳健的机制。特别是，在2D上皮层，我们表明，动态异质性的机制，避免了一些病理依赖性，破坏模型的基础上，分层干/祖组织。
To maintain cycling adult tissue in homeostasis the balance between proliferation and differentiation of stem cells needs to be precisely regulated. To investigate how stem cells achieve perfect self-renewal, emphasis has been placed on models in which stem cells progress sequentially through a one-way proliferative hierarchy. However, investigations of tissue regeneration have revealed a surprising degree of flexibility, with cells normally committed to differentiation able to recover stem cell competence following injury. Here, we investigate whether the reversible transfer of cells between states poised for proliferation or differentiation may provide a viable mechanism for a heterogeneous stem cell population to maintain homeostasis even under normal physiological conditions. By addressing the clonal dynamics, we show that such models of "dynamic heterogeneity" may be equally capable of describing the results of recent lineage tracing assays involving epithelial tissues. Moreover, together with competition for limited niche access, such models may provide a mechanism to render tissue homeostasis robust. In particular, in 2D epithelial layers, we show that the mechanism of dynamic heterogeneity avoids some pathological dependencies that undermine models based on a hierarchical stem/ progenitor organization.