Conversion of human fibroblasts into functional Leydig-like cells by small molecules and a single factor
Conversion of human fibroblasts into functional Leydig-like cells by small molecules and a single factor
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小分子和单因子将人成纤维细胞转化为功能性Leydig样细胞
DOI：
10.1016/j.bbrc.2019.05.178
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发表时间：
2019
影响因子：
3.1
通讯作者：
Jie Sun
中科院分区：
文献类型：
--
作者：
Jin Zhou;Yanping Hou;Zhiyuan Zhang;Xiaoyu Xing;Xiangyu Zou;Liang Zhong;Hua Huang;Zhen Zhang;Jie Sun
将成纤维细胞重编程为间质细胞（LCs）为男性性腺功能减退症的细胞治疗提供了一个有希望的来源。最近，通过强制表达多个转录因子（tf）来实现。然而，为了最终的安全和方便的应用，小分子将是一种革命性的和理想的方法来减少或消除基因操作。在这里，我们报告了一种确定的小分子鸡尾酒，它可以仅用一种转录因子就能高效地将人成纤维细胞转化为功能性lc。这些诱导细胞在形态、标记基因表达和睾酮分泌功能方面与人LCs相似。该研究为未来的药理学重编程奠定了基础，并为研究重编程的机制提供了一个独特的场所。
Reprogramming fibroblasts into Leydig cells (LCs) offers a promising source for cell-based therapy for male hypogonadism. Recently, it has been achieved by forced expression of multiple transcription factors (TFs). However, for ultimate safe and convenient application, small molecules would be a revolutionary and desirable method to reduce or eliminate the genetic manipulations. Here, we report a defined small-molecule cocktail that enables the highly efficient conversion of human fibroblasts into functional LCs with only one transcription factor. These induced cells resembled human LCs with respect to morphology, marker gene expression and secretary function of testosterone. This study lays a foundation for future pharmacological reprogramming and provides a unique venue for investigating mechanisms underlying reprogramming.