Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, 92697, USA.
Department of Mathematics, University of California, Irvine, Irvine, CA, 92697, USA.
Nat Commun. 2020 Aug 25;11(1):4239. doi: 10.1038/s41467-020-18075-7.
How stem cells give rise to epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations at the top and bottom of rete ridges and transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling suggests that basal cell populations serve as crucial signaling hubs to maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest that transitional basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed transitional basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.
尽管表皮在形成屏障和附属物方面起着至关重要的作用，但干细胞如何产生表皮仍不清楚。在这里，我们使用单细胞 RNA 测序来探究人毛囊间表皮的基底干细胞异质性，发现在网嵴的顶部和底部以及基底层和上基底层之间的过渡位置存在四个空间上不同的干细胞群体。细胞间通讯建模表明，基底细胞群体作为维持表皮通讯的关键信号枢纽。结合拟时、RNA 速度和细胞熵分析表明，分层分化谱系支持多干细胞毛囊间表皮稳态模型，并表明过渡性基底干细胞是维持适当分层所必需的稳定状态。最后，差异表达的过渡性基底干细胞基因的改变导致人类皮肤等效物严重变薄，验证了它们在表皮稳态中的重要作用，并强调了基底干细胞异质性的关键性质。
