真皮乳头细胞衍生的外泌体通过 LEF1 调节毛囊干细胞增殖。
Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1.
机构信息
College of Animal Science and Technology, Yangzhou University, 48 South University Ave Yangzhou, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, 48 South University Ave Yangzhou, Yangzhou 225009, China.
出版信息
Int J Mol Sci. 2023 Feb 16;24(4):3961. doi: 10.3390/ijms24043961.
Hair follicle (HF) growth and development are controlled by various cell types, including hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Exosomes are nanostructures that participate in many biological processes. Accumulating evidence indicates that DPC-derived exosomes (DPC-Exos) mediate HFSC proliferation and differentiation during the cyclical growth of hair follicles. In this study, we found that DPC-Exos increase ki67 expression and CCK8 cell viability readouts in HFSCs but reduce annexin staining of apoptotic cells. RNA sequencing of DPC-Exos-treated HFSCs identified 3702 significantly differentially expressed genes (DEGs), including , , , , , and . These DEGs were enriched in HF growth- and development-related pathways. We further verified the function of LEF1 and showed that overexpression of LEF1 increased the expression of HF development-related genes and proteins, enhanced HFSC proliferation, and reduced HFSC apoptosis, while knockdown of LEF1 reversed these effects. DPC-Exos could also rescue the siRNA-LEF1 effect in HFSCs. In conclusion, this study demonstrates that DPC-Exos mediated cell-to-cell communication can regulate HFSCs proliferation by stimulating LEF1 and provide novel insights into HF growth and development regulatory mechanisms.
毛囊（HF）的生长和发育受到多种细胞类型的控制，包括毛囊干细胞（HFSCs）和真皮乳头细胞（DPCs）。外泌体是参与许多生物学过程的纳米结构。越来越多的证据表明，真皮乳头细胞衍生的外泌体（DPC-Exos）在毛囊周期性生长过程中介导毛囊干细胞的增殖和分化。在这项研究中，我们发现 DPC-Exos 增加了 HFSCs 中的 ki67 表达和 CCK8 细胞活力读数，但减少了凋亡细胞的 Annexin 染色。用 DPC-Exos 处理的 HFSCs 的 RNA 测序鉴定出 3702 个明显差异表达的基因（DEGs），包括 、 、 、 、 和 。这些 DEGs 富集在 HF 生长和发育相关途径中。我们进一步验证了 LEF1 的功能，并表明过表达 LEF1 增加了 HF 发育相关基因和蛋白的表达，增强了 HFSC 的增殖，减少了 HFSC 的凋亡，而 LEF1 的敲低则逆转了这些效应。DPC-Exos 还可以挽救 HFSCs 中的 siRNA-LEF1 效应。总之，这项研究表明，DPC-Exos 介导的细胞间通讯可以通过刺激 LEF1 来调节 HFSCs 的增殖，并为 HF 的生长和发育调控机制提供新的见解。
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