Adult neurogenesis in the olfactory epithelium is often depicted as a unidirectional pathway during homeostasis and repair. We challenge the unidirectionality of this model by showing that epithelial injury unlocks the potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to dedifferentiate into multipotent stem/progenitor cells that contribute significantly to tissue regeneration in the murine olfactory epithelium (OE). We characterize these dedifferentiating cells using several lineage-tracing strains and single-cell mRNA-seq, and we show that Sox2 is required for initiating dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor expansion. These results suggest that the apparent hierarchy of neuronal differentiation is not irreversible and that lineage commitment can be overridden following severe tissue injury. We elucidate a previously unappreciated pathway for endogenous tissue repair by a highly regenerative neuroepithelium and introduce a system to study the mechanisms underlying plasticity in the OE that can be adapted for other tissues.

中文翻译：

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损伤诱导神经元祖细胞内源性重编程和去分化为多能。

嗅觉上皮细胞中的成人神经发生通常被描述为体内稳态和修复过程中的单向途径。我们通过显示上皮损伤释放了Ascl1 +祖细胞和Neurog1 +指定的神经元前体去分化为能对鼠嗅上皮（OE）显着促进组织再生的多能干/祖细胞的潜力，从而挑战了该模型的单向性。我们使用几种谱系追踪株和单细胞mRNA-seq来表征这些去分化细胞，并且我们表明Sox2是启动去分化所必需的，抑制Ezh2可以促进多能祖细胞的扩增。这些结果表明，神经元分化的明显层次不是不可逆的，并且在严重的组织损伤后，血统承诺可以被取代。我们阐明了通过高度再生的神经上皮细胞进行内源性组织修复的先前未曾了解的途径，并介绍了一种系统来研究可用于其他组织的OE中可塑性的机制。