Notch1 down-regulation in lineage-restricted niches is involved in the development of mouse eccrine sweat glands
Notch1 down-regulation in lineage-restricted niches is involved in the development of mouse eccrine sweat glands
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DOI：
10.1007/s10735-022-10098-2
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发表时间：
2022-08
影响因子：
3.2
通讯作者：
Yuzhen Wang;B. Yao;Xianlan Duan;Jianjun Li;W. Song;Enhejirigala;Zhao Li;X. Yuan;Yi Kong;Yijie Zhang;Xiao-Bo Fu;Sha Huang
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作者：
Yuzhen Wang;B. Yao;Xianlan Duan;Jianjun Li;W. Song;Enhejirigala;Zhao Li;X. Yuan;Yi Kong;Yijie Zhang;Xiao-Bo Fu;Sha Huang
小汗腺（SG）仅存在于小鼠足垫中，表明小鼠足底真皮（PD）包含 SG 谱系限制的生态位。然而，目前尚不清楚这些生态位如何影响干细胞向 SG 的命运。在这项研究中，我们试图找到干细胞在体内和体外感知 SG 谱系特异性生态位并与之相互作用的关键线索。首先，我们利用转录组RNA测序分析筛选SG细胞和表皮干细胞（ES）之间的差异表达基因，并利用蛋白质组学分析筛选PD和真皮背侧（DD）之间的差异表达蛋白。根据基因本体（GO）富集分析，发现Notch1在基因和蛋白质水平上都有差异表达，并且与SG形态发生密切相关。其次，检测Notch1在SG胚胎和产后发育过程中的时空变化。第三，将小鼠间充质干细胞（MSC）体外导入SG样细胞中，以进一步验证Notch1的可能作用。结果显示，Notch1随着体内SG形态发生的过程以及体外MSCs分化为SG样细胞的过程而持续下调。因此，我们认为Notch1可能在SG发育过程中充当“看门人”的角色，并调节干细胞和SG谱系特异性生态位之间的相互作用。这项研究可能有助于了解胚胎 SG 器官发生的机制。
Eccrine sweat gland (SG) restrictedly exists in mouse foot pads indicating that mouse plantar dermis (PD) contains the SG lineage-restricted niches. However, it is still unclear how these niches can affect stem cell fate towards SG. In this study, we tried to find the key cues by which stem cells sense and interact with the SG lineage-specific niches both in vivo and in vitro. Firstly, we used transcriptomics RNA sequencing analysis to screen differentially expressed genes between SG cells and epidermal stem cells (ES), and used proteomic analysis to screen differentially expressed proteins between PD and dorsal dermis (DD). Notch1 was found differentially expressed in both gene and protein levels, and was closely related to SG morphogenesis based on Gene Ontology (GO) enrichment analysis. Secondly, the spatial-temporal changes of Notch1 during embryonic and post-natal development of SG were detected. Thirdly, mouse mesenchymal stem cells (MSCs) were introduced into SG-like cells in vitro in order to further verify the possible roles of Notch1. Results revealed that Notch1 was continuously down-regulated along with the process of SG morphogenesis in vivo, and also along with the process that MSCs differentiated into SG-like cells in vitro. Hence, we suggest that Notch1 possibly acts as with roles of “gatekeeper” during SG development and regulates the interactions between stem cells and the SG lineage-specific niches. This study might help for understanding mechanisms of embryonic SG organogenesis.