Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Dermatology, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, China.
Biosci Trends. 2020 May 21;14(2):104-114. doi: 10.5582/bst.2019.01345. Epub 2020 Apr 23.
Transcultured human skin derived precursors (tSKPs) from adherent monolayer culture system have similar characteristics as traditional skin derived precursors (SKPs), making tSKPs a suitable candidate for regenerative medicine. tSKPs can differentiate into fibroblasts. However, little is known about the molecular mechanism of the transition from tSKPs to fibroblasts. Here, we compared the transcriptional profiles of human tSKPs and tSKPs-derived fibroblasts (tFBs) by RNA-Sequence aiming to determine the candidate genes and pathways involving in the differentiation process. A total of 1042 differentially expressed genes (DEGs) were identified between tSKPs and tFBs, with 490 genes up-regulated and 552 genes down-regulated. Our study showed that these DEGs were significantly enriched in tumor necrosis factor signaling pathway, focal adhesion, extracellular matrix-receptor interaction and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. A further transcription factors (TFs) analysis of DEGs revealed the significantly down-expressed TFs (p21, Foxo1and Foxc1) in tFBs were mostly the downstream nodes of PI3K-Akt signaling pathway, which suggested PI3K-Akt signaling pathway might play an important role in tSKPs differentiation. The results of our study are useful for investigating the molecular mechanisms in tSKPs differentiation into tFBs, making it possible to take advantage of their potential application in regenerative medicine.
从贴壁单层培养体系中获得的人源诱导多能干细胞前体细胞(tSKPs)具有与传统皮肤来源前体细胞(SKPs)相似的特征,这使得 tSKPs 成为再生医学的候选者。tSKPs 可以分化为成纤维细胞。然而,关于 tSKPs 向成纤维细胞转化的分子机制知之甚少。在这里,我们通过 RNA 测序比较了人 tSKPs 和 tSKPs 衍生的成纤维细胞(tFBs)的转录谱,旨在确定涉及分化过程的候选基因和途径。在 tSKPs 和 tFBs 之间鉴定出了 1042 个差异表达基因(DEGs),其中 490 个基因上调,552 个基因下调。我们的研究表明,这些 DEGs 显著富集在肿瘤坏死因子信号通路、粘着斑、细胞外基质-受体相互作用和磷脂酰肌醇 3 激酶(PI3K)/蛋白激酶 B(Akt)信号通路。进一步对 DEGs 的转录因子(TFs)分析表明,在 tFBs 中显著下调的 TFs(p21、Foxo1 和 Foxc1)大多是 PI3K-Akt 信号通路的下游节点,这表明 PI3K-Akt 信号通路可能在 tSKPs 分化中发挥重要作用。我们的研究结果有助于研究 tSKPs 分化为 tFBs 的分子机制,从而有可能利用它们在再生医学中的潜在应用。