Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA, Beijing, 100853, P.R. China.
Key Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Fourth Medical Center of PLA General Hospital, Beijing, 100048, P.R. China.
Cell Death Dis. 2019 Mar 20;10(4):272. doi: 10.1038/s41419-019-1503-7.
Several studies have reported inducing adult cells into sweat gland-like cells; however, slow transition and low efficiency limit the potential for cell-based treatment. Here, we show that overexpression of the transcription factor FoxC1 was sufficient to reprogram epidermal cells to induced functional sweat gland-like cells (iSGCs). The iSGCs expressing secreting-related genes, had a global gene expression profile between fetal SGCs (P5) and adult SGCs (P28). Moreover, iSGCs transplanted into the burn mice model facilitated wound repair and sweat gland regeneration. We further demonstrated that the Foxc1 upregulated BMP5 transcription and BMP5 is responsible for the cell-type transition. Collectively, this study shows that lineage reprogramming of epidermal cells into iSGCs provides an excellent cell source and a promising regenerative strategy for anhidrosis and hypohidrosis.
已有多项研究报道了诱导成体细胞向汗腺样细胞分化的方法，但细胞转化速度慢、效率低，限制了细胞治疗的潜力。本研究表明，转录因子 FoxC1 的过表达足以将表皮细胞重编程为诱导功能性汗腺样细胞（iSGCs）。iSGCs 表达分泌相关基因，其基因表达谱介于胎鼠 SGCs（P5）和成鼠 SGCs（P28）之间。此外，将 iSGCs 移植到烧伤小鼠模型中，可促进伤口修复和汗腺再生。我们进一步证明，Foxc1 上调了 BMP5 的转录，而 BMP5 负责细胞类型的转变。综上，本研究表明，表皮细胞向 iSGCs 的谱系重编程为无汗症和少汗症提供了一个极好的细胞来源和有前途的再生策略。
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