Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.
Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.
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DOI：
10.1016/j.stem.2017.04.003
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发表时间：
2017-06-01
期刊：
影响因子：
23.9
通讯作者：
Ngai J
中科院分区：
文献类型：
--
作者：
Fletcher RB;Das D;Gadye L;Street KN;Baudhuin A;Wagner A;Cole MB;Flores Q;Choi YG;Yosef N;Purdom E;Dudoit S;Risso D;Ngai J
详细了解干细胞产生成熟后代的路径对于阐明控制细胞命运决定和组织稳态的机制至关重要。成体干细胞在嗅觉上皮中维持和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，定义出生后嗅上皮的详细图谱，揭示嗅觉干细胞谱系轨迹中的细胞命运潜力和分支点。嗅觉干细胞在没有细胞分裂的情况下通过直接命运转换产生支持细胞，它们在群体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选择来调节干细胞命运。这种综合方法揭示了引导嗅觉谱系轨迹的机制，并提供了一个解构其他干细胞生态位中类似层次结构的模型。
A detailed understanding of the paths that stem cells traverse to generate mature progeny is vital for elucidating 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 branch points 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 mechanisms guiding olfactory lineage trajectories and provides a model for deconstructing similar hierarchies in other stem cell niches.