A detailed understanding of the paths that stem cells traverse to generate mature progeny is vital for elucidating the mechanisms governing cell fate decisions and tissue homeostasis. Adult stem cells maintain and regenerate multiple mature cell lineages in the olfactory epithelium. Here we integrate single-cell RNA sequencing and robust statistical analyses with in vivo lineage tracing to define a detailed map of the postnatal olfactory epithelium, revealing cell fate potentials and branchpoints in olfactory stem cell lineage trajectories. Olfactory stem cells produce support cells via direct fate conversion in the absence of cell division, and their multipotency at the population level reflects collective unipotent cell fate decisions by single stem cells. We further demonstrate that Wnt signaling regulates stem cell fate by promoting neuronal fate choices. This integrated approach reveals the mechanisms guiding olfactory lineage trajectories and provides a model for deconstructing similar hierarchies in other stem cell niches.

中文翻译：

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以单细胞分辨率解构嗅觉干细胞轨迹。

对干细胞横穿以生成成熟后代的途径的详细了解对于阐明控制细胞命运决定和组织稳态的机制至关重要。成年干细胞在嗅觉上皮细胞中维持并再生多个成熟细胞谱系。在这里，我们将单细胞RNA测序和强大的统计分析与体内谱系追踪相结合，以定义产后嗅觉上皮细胞的详细图谱，揭示嗅觉干细胞谱系轨迹中的细胞命运潜力和分支点。嗅觉干细胞在不存在细胞分裂的情况下通过直接命运转换来产生支持细胞，它们在种群水平上的多能性反映了单个干细胞的集体单能细胞命运决定。我们进一步证明Wnt信号通过促进神经元命运的选择来调节干细胞的命运。这种综合的方法揭示了指导嗅觉谱系轨迹的机制，并提供了一个模型来解构其他干细胞生态位中的类似层次结构。