Single-Cell Analysis Reveals a Hair Follicle Dermal Niche Molecular Differentiation Trajectory that Begins Prior to Morphogenesis
Single-Cell Analysis Reveals a Hair Follicle Dermal Niche Molecular Differentiation Trajectory that Begins Prior to Morphogenesis
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DOI：
10.1016/j.devcel.2018.11.032
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发表时间：
2019-01-07
影响因子：
11.8
通讯作者：
Myung, Peggy
中科院分区：
文献类型：
--
作者：
Gupta, Khusali;Levinsohn, Jonathan;Myung, Peggy
由于无法区分缺乏组织学区分的细胞之间的定量分子差异，描述附属物形态发生之前的分子和细胞事件一直具有挑战性。毛囊（HF）真皮凝析液（DC）是一群对HF发育和再生至关重要的细胞。人们对预示这一独特种群出现的事件知之甚少。使用无偏单细胞RNA测序和体内方法，我们推断出DC细胞在HF形态发生之前开始传递的转录状态序列。我们的数据表明，Wnt/ β -连环蛋白信号传导需要进入静止和分化之前的中间阶段。此外，我们提供的证据表明，静止的DC细胞是在形态发生之前存在的选择性增殖细胞的后代，这些细胞后来在DC扩张期间在DC周围区域被发现。总之，这些发现提供了导致DC细胞分化的分子状态的推断路径。
Delineating molecular and cellular events that precede appendage morphogenesis has been challenging due to the inability to distinguish quantitative molecular differences between cells that lack histological distinction. The hair follicle (HF) dermal condensate (DC) is a cluster of cells critical for HF development and regeneration. Events that presage emergence of this distinctive population are poorly understood. Using unbiased single-cell RNA sequencing and in vivo methods, we infer a sequence of transcriptional states through which DC cells pass that begins prior to HF morphogenesis. Our data indicate that Wnt/beta-catenin signaling is required to progress into an intermediate stage that precedes quiescence and differentiation. Further, we provide evidence that quiescent DC cells are recent progeny of selectively proliferating cells present prior to morphogenesis and that are later identified in the peri-DC zone during DC expansion. Together, these findings provide an inferred path of molecular states that lead to DC cell differentiation.