Nature ( IF 42.778 ) Pub Date : 2021-06-09 , DOI: 10.1038/s41586-021-03638-5 Ritsuko Morita, Noriko Sanzen, Hiroko Sasaki, Tetsutaro Hayashi, Mana Umeda, Mika Yoshimura, Takaki Yamamoto, Tatsuo Shibata, Takaya Abe, Hiroshi Kiyonari, Yasuhide Furuta, Itoshi Nikaido, Hironobu Fujiwara
Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events1,2. 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 suggested3). 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 insects4,5, 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.
组织干细胞是通过器官特异性形态发生事件从一群胚胎祖细胞中产生的1,2. 尽管组织干细胞是器官稳态和再生的核心，但它们在发育过程中如何被诱导仍不清楚，主要是因为缺乏专门标记预期干细胞的标记物。在这里，我们结合了独立于标记物的长期 3D 实时成像和单细胞转录组学，以捕捉小鼠毛囊整个上皮在发育过程中的动态谱系进展和转录组变化。我们发现不同上皮谱系的前体在头发基板的基底层中以二维同心方式排列。每个同心环获得独特的转录组并延伸形成纵向排列的 3D 圆柱形隔室。预期的膨出干细胞来自基板基底层的外围环，3）。基板细胞的命运由细胞位置决定，而不是由细胞分裂的方向决定。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图谱，与细胞谱系数据一致。将这些发现与之前关于昆虫附属物发育的工作4,5相结合，我们描述了“望远镜模型”，这是一种外胚层器官发育的通用模型，其中基板中的 2D 同心区望远镜形成 3D 纵向排列的圆柱形隔间。