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.

中文翻译：

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损伤可激活具有不同谱系能力的瞬态嗅觉干细胞状态。

成人体内干细胞的更新和分化程序介导了组织的稳态和再生。然而，在如此广泛变化的条件下调节干细胞命运的机制尚不完全清楚。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，并跟踪了在再生小鼠嗅觉上皮细胞中使用稀疏谱系描记的干细胞衍生克隆的成熟度。受伤后，静止的嗅觉干细胞迅速转变为活化的，短暂的状态，这种状态是再生所特有的，并经过定制以满足损伤诱导修复的需求，包括屏障形成和增殖。在激活的这个早期窗口期间，指定了多种细胞命运，包括更新的干细胞和确定的分化祖细胞。我们进一步表明，Sox2对于细胞从激活的祖先状态过渡到神经元祖先状态至关重要。我们的研究突出了干细胞介导的再生策略，该策略可能在其他成年干细胞壁may中得以保留。