Fletcher Russell B, Das Diya, Gadye Levi, Street Kelly N, Baudhuin Ariane, Wagner Allon, Cole Michael B, Flores Quetzal, Choi Yoon Gi, Yosef Nir, Purdom Elizabeth, Dudoit Sandrine, Risso Davide, Ngai John
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
Cell Stem Cell. 2017 Jun 1;20(6):817-830.e8. doi: 10.1016/j.stem.2017.04.003. Epub 2017 May 11.
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.
深入了解干细胞生成成熟子代所经历的途径，对于阐明控制细胞命运决定和组织稳态的机制至关重要。成体干细胞维持并再生嗅觉上皮中的多种成熟细胞谱系。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，以定义出生后嗅觉上皮的详细图谱，揭示嗅觉干细胞谱系轨迹中的细胞命运潜能和分支点。嗅觉干细胞在不进行细胞分裂的情况下通过直接命运转换产生支持细胞，并且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指导嗅觉谱系轨迹的机制，并为解构其他干细胞微环境中的类似层级结构提供了一个模型。
