Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage Capacities.
Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage Capacities.
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DOI：
10.1016/j.stem.2017.10.014
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发表时间：
2017-12-07
期刊：
影响因子：
23.9
通讯作者：
Fletcher RB
中科院分区：
文献类型：
--
作者：
Gadye L;Das D;Sanchez MA;Street K;Baudhuin A;Wagner A;Cole MB;Choi YG;Yosef N;Purdom E;Dudoit S;Risso D;Ngai J;Fletcher RB
组织稳态和再生是由成体干细胞更新和分化程序介导的。然而，在如此广泛变化的条件下调节干细胞命运的机制尚未完全了解。使用单细胞技术，我们评估了与干细胞自我更新和分化相关的转录变化，并在再生小鼠嗅上皮中使用稀疏谱系追踪跟踪干细胞衍生克隆的成熟。损伤后，静止的嗅觉干细胞迅速转变为激活的、短暂的再生状态，以满足损伤诱导的修复需求，包括屏障的形成和增殖。多种细胞命运——包括再生的干细胞和承诺分化的祖细胞——在这一激活的早期窗口期被指定。我们进一步证明Sox2对于细胞从激活状态过渡到神经元祖细胞状态至关重要。我们的研究强调了干细胞介导的再生策略，这些策略可能在其他成体干细胞壁龛中保守。Gadye等人利用多个单细胞技术鉴定了在损伤诱导的嗅觉上皮再生过程中干细胞自我更新和分化的细胞状态转变。嗅觉干细胞大量转移到一种短暂的细胞状态，这种状态是再生所特有的，在这种状态下，不同的命运被指定。
Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation. Multiple cell fates – including renewed stem cells and committed differentiating progenitors – are specified during this early window of activation. We further show that Sox2 is essential for cells to transition from the activated to neuronal progenitor states. Our study highlights strategies for stem cell-mediated regeneration that may be conserved in other adult stem cell niches. Gadye et al. use multiple single cell techniques to identify the cell state transitions underlying the stem cell self-renewal and differentiation during injury-induced regeneration of the olfactory epithelium. Olfactory stem cells shift en masse to a transient cell state unique to regeneration in which diverse fates are specified.
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影响因子：
14.9
作者：
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发表时间：
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