期刊
STEM CELL REPORTS
卷 15, 期 2, 页码 408-423出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2020.07.002
关键词
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资金
- National Natural Science Foundation of China [81871150, 31801235]
- Natural Science Foundation of Guangdong Province [2018A030313473, 2015A030310132]
- Science and Technology Plan Project of Guangzhou [201803010044, 201704YG066, 202002030168]
- Major Scientific and Technological Special Project ofAdministration of Ocean and Fisheries of Guangdong Province
- China Postdoctoral Science Foundation [2017M622914]
Recent studies have demonstrated that fibroblasts can be directly converted into functional Leydig cells by transcription factors. How-ever, the transgenic approach used in these studies raises safety concerns for its future application. Here, we report that fibroblasts can be directly reprogrammed into Leydig-like cells by exposure to a combination of forskolin, 20 alpha-hydroxycholesterol, luteinizing hormone, and SB431542. These chemical compound-induced Leydig-like cells (CiLCs) express steroidogenic genes and have a global gene expres-sion profile similar to that of progenitor Leydig cells, although not identical. In addition, these cells can survive in testis and produce testosterone in a circadian rhythm. This induction strategy is applicable to reprogramming human periodontal ligament fibroblasts to-ward Leydig-like cells. These findings demonstrated fibroblasts can be directly converted into Leydig-like cells by pure chemical com-pounds. This strategy overcomes the limitations of conventional transgenic-based reprogramming and provides a simple, effective approach for Leydig cell-based therapy while simultaneously preserving the hypothalamic-pituitary-gonadal axis.
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