High-resolution single-cell transcriptomics reveals heterogeneity of self-renewing hair follicle stem cells.
High-resolution single-cell transcriptomics reveals heterogeneity of self-renewing hair follicle stem cells.
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DOI：
10.1111/exd.14262
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发表时间：
2021-04
影响因子：
3.6
通讯作者：
Tumbar T
中科院分区：
文献类型：
--
作者：
Chovatiya G;Ghuwalewala S;Walter LD;Cosgrove BD;Tumbar T
多能凸起干细胞（SC）在成人皮肤稳态过程中促进毛囊（HF）循环生长，但其内在的分子异质性尚不清楚。这些毛囊干细胞 (HFSC) 在毛发周期中参与自我更新、迁移和分化。在这里，我们对处于生长期中期（自我更新阶段）的小鼠皮肤中分类为 CD34+/K14-H2BGFP+ 的 HFSC 进行高分辨率单细胞 RNA 测序 (scRNA-seq)。我们剖析转录组谱并揭示群体特异性转录异质性。无监督聚类揭示了 5 个主要 HFSC 种群，它们通过与下面的凸起和外根鞘 (ORS) 相关的已知标记来区分。这些群体包括静止凸出细胞、ORS 细胞状态和增殖细胞。谱系轨迹分析预测了这些细胞状态及其相应的自我更新亚群的预期分化路径。凸起群体本身可以进一步细分为不同的子群体，这些子群体可以映射到上、中和下凸起区域，并呈现递减的静止分数。基因集富集分析 (GSEA) 揭示了新的标记，并表明 ORS 和 bulge 亚群的潜在不同功能。这包括上凸起亚群和感觉神经之间以及上 ORS 和皮肤脉管系统之间的通信，以及细胞迁移功能中凸起子集的丰富。较低的ORS富集基因可能使营养物质从周围的脂肪和脉管系统细胞传递到增殖的毛基质细胞。因此，我们对 HFSC 自我更新阶段的分子异质性进行了全面的描述，这使得未来的 HF 功能研究成为可能。
Multipotent bulge stem cells (SCs) fuel the hair follicle (HF) cyclic growth during adult skin homeostasis, but their intrinsic molecular heterogeneity is not well understood. These hair follicle stem cells (HFSCs) engage in bouts of self-renewal, migration, and differentiation during the hair cycle. Here we perform high resolution single-cell RNA sequencing (scRNA-seq) of HFSCs sorted as CD34+/K14-H2BGFP+ from mouse skin at mid-anagen, the self-renewal stage. We dissect the transcriptomic profiles and unravel population-specific transcriptional heterogeneity. Unsupervised clustering reveals 5 major HFSC populations, which, distinguished by known markers associated with both the bulge and the outer root sheath (ORS) underneath. These populations include quiescent bulge, ORS cellular states, and proliferative cells. Lineage trajectory analysis predicted the prospective differentiation path of these cellular states and their corresponding self-renewing subpopulations. The bulge population itself can be further sub-divided into distinct subpopulations that can be mapped to the upper, mid, and lower bulge regions, and present a decreasing quiescence score. Gene set enrichment analysis (GSEA) revealed new markers and suggested potentially distinct functions of the ORS and bulge subpopulations. This included communications between the upper bulge subpopulation and sensory nerves and between the upper ORS and skin vasculature, as well as enrichment of a bulge subset in cell migratory functions. The lower ORS enriched genes may potentially enable nutrients passing from the surrounding fat and vasculature cells towards the proliferating hair matrix cells. Thus, we provide a comprehensive account of HFSC molecular heterogeneity during their self-renewing stage, which enables future HF functional studies.
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DOI：
10.1002/stem.2868
发表时间：
2018-10
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Jain P;Nattakom M;Holowka D;Wang DH;Thomas Brenna J;Ku AT;Nguyen H;Ibrahim SF;Tumbar T
通讯作者：
Tumbar T
影响因子：
23.9
作者：
Joost, Simon;Annusver, Karl;Kasper, Maria
通讯作者：
Kasper, Maria
影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
影响因子：
23.9
作者：
Brownell, Isaac;Guevara, Elizabeth;Bai, C. Brian;Loomis, Cynthia A.;Joyner, Alexandra L.
通讯作者：
Joyner, Alexandra L.
影响因子：
11.2
作者：
Huang WY;Lai SF;Chiu HY;Chang M;Plikus MV;Chan CC;Chen YT;Tsao PN;Yang TL;Lee HS;Chi P;Lin SJ
通讯作者：
Lin SJ