Single-Cell RNA Profiling of Human Skin Reveals Age-Related Loss of Dermal Sheath Cells and Their Contribution to a Juvenile Phenotype.
Single-Cell RNA Profiling of Human Skin Reveals Age-Related Loss of Dermal Sheath Cells and Their Contribution to a Juvenile Phenotype.
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DOI：
10.3389/fgene.2021.797747
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发表时间：
2021
影响因子：
3.7
通讯作者：
Siracusa A
中科院分区：
文献类型：
--
作者：
Ahlers JMD;Falckenhayn C;Holzscheck N;Solé-Boldo L;Schütz S;Wenck H;Winnefeld M;Lyko F;Grönniger E;Siracusa A
真皮鞘（DS）是一群间充质来源的皮肤细胞，对皮肤稳态具有重要意义。DS包括毛囊真皮干细胞，其表现出自我更新并作为毛乳头（DP）细胞和DS细胞的双能祖细胞。随着年龄的增长，干细胞在自我更新方面表现出缺陷，并且它们的数量减少。虽然已经相当详细地检查了小鼠的DS，但我们对人类DS的了解非常有限，有助于其自我更新和分化能力的途径以及对组织再生和衰老重要的潜在旁分泌作用。使用来自不同年龄供体的人类皮肤活检的单细胞RNA测序，我们现在已经分析了72，048个细胞的转录组，包括50，149个成纤维细胞。我们的研究结果表明，表现出干细胞特征的DS细胞在衰老时丢失。我们进一步表明，HES1，COL11A1，MYL4和CTNNB1调节DS干细胞特性。最后，DS分泌的蛋白激活素A显示对角质形成细胞和真皮成纤维细胞的旁分泌作用，促进增殖、表皮厚度和前胶原产生。我们的工作提供了一个详细的描述，人类DS身份的单细胞水平上，其老化后的损失，其干细胞的特点和它的贡献，青少年皮肤表型。
The dermal sheath (DS) is a population of mesenchyme-derived skin cells with emerging importance for skin homeostasis. The DS includes hair follicle dermal stem cells, which exhibit self-renewal and serve as bipotent progenitors of dermal papilla (DP) cells and DS cells. Upon aging, stem cells exhibit deficiencies in self-renewal and their number is reduced. While the DS of mice has been examined in considerable detail, our knowledge of the human DS, the pathways contributing to its self-renewal and differentiation capacity and potential paracrine effects important for tissue regeneration and aging is very limited. Using single-cell RNA sequencing of human skin biopsies from donors of different ages we have now analyzed the transcriptome of 72,048 cells, including 50,149 fibroblasts. Our results show that DS cells that exhibit stem cell characteristics were lost upon aging. We further show that HES1, COL11A1, MYL4 and CTNNB1 regulate DS stem cell characteristics. Finally, the DS secreted protein Activin A showed paracrine effects on keratinocytes and dermal fibroblasts, promoting proliferation, epidermal thickness and pro-collagen production. Our work provides a detailed description of human DS identity on the single-cell level, its loss upon aging, its stem cell characteristics and its contribution to a juvenile skin phenotype.
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影响因子：
11.8
作者：
Shin, Wisoo;Rosin, Nicole L.;Biernaskie, Jeff
通讯作者：
Biernaskie, Jeff
影响因子：
64.8
作者：
Reynolds, AJ;Lawrence, C;Jahoda, CAB
通讯作者：
Jahoda, CAB
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
1.5
作者：
Huth, Laura;Marquardt, Yvonne;Huth, Sebastian
通讯作者：
Huth, Sebastian
影响因子：
64.8
作者：
La Manno G;Soldatov R;Zeisel A;Braun E;Hochgerner H;Petukhov V;Lidschreiber K;Kastriti ME;Lönnerberg P;Furlan A;Fan J;Borm LE;Liu Z;van Bruggen D;Guo J;He X;Barker R;Sundström E;Castelo-Branco G;Cramer P;Adameyko I;Linnarsson S;Kharchenko PV
通讯作者：
Kharchenko PV