Tracing the origin of hair follicle stem cells
Tracing the origin of hair follicle stem cells
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DOI：
10.1038/s41586-021-03638-5
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发表时间：
2021-06-09
期刊：
影响因子：
64.8
通讯作者：
Fujiwara, Hironobu
中科院分区：
文献类型：
--
作者：
Morita, Ritsuko;Sanzen, Noriko;Fujiwara, Hironobu
组织干细胞通过器官特异性形态发生事件从胚胎祖细胞群体产生（1，2）。虽然组织干细胞是器官稳态和再生的核心，但仍不清楚它们在发育过程中是如何被诱导的，主要是因为缺乏专门标记未来干细胞的标记物。在这里，我们结合联合收割机标记独立的长期三维实时成像和单细胞转录组学捕捉动态谱系进展和转录组的变化，在整个上皮细胞的小鼠毛囊，因为它的发展。我们发现，不同的上皮细胞系的前体排列在一个二维同心的方式在基底层的毛基板。每个同心环获得独特的转录组，并延伸形成纵向对齐的3D圆柱形隔室。预期的隆突干细胞来源于基板基底层的外周环，而不是来自基底上细胞（如先前所建议的（3））。基板细胞的命运是由细胞位置决定的，而不是由细胞分裂的方向决定的。我们还确定了13个基因簇：这些簇的整体表达动态绘制了上皮谱系多样化的整个转录景观，与细胞谱系数据一致。结合这些发现与以前的工作在昆虫的附属物的发展（4，5），我们描述了“望远镜模型”，外胚层器官的发展，其中二维同心区在基板望远镜出来，形成三维纵向排列的圆柱形隔间的广义模型。
Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events(1,2). Although tissue stem cells are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly because of the lack of markers that exclusively label prospective stem cells. Here we combine marker-independent long-term 3D live imaging and single-cell transcriptomics to capture a dynamic lineage progression and transcriptome changes in the entire epithelium of the mouse hair follicle as it develops. We found that the precursors of different epithelial lineages were aligned in a 2D concentric manner in the basal layer of the hair placode. Each concentric ring acquired unique transcriptomes and extended to form longitudinally aligned, 3D cylindrical compartments. Prospective bulge stem cells were derived from the peripheral ring of the placode basal layer, but not from suprabasal cells (as was previously suggested(3)). The fate of placode cells is determined by the cell position, rather than by the orientation of cell division. We also identified 13 gene clusters: the ensemble expression dynamics of these clusters drew the entire transcriptional landscape of epithelial lineage diversification, consistent with cell lineage data. Combining these findings with previous work on the development of appendages in insects(4,5), we describe the 'telescope model', a generalized model for the development of ectodermal organs in which 2D concentric zones in the placode telescope out to form 3D longitudinally aligned cylindrical compartments.