Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation

Proceedings of the National Academy of Sciences of the United States of America
Lianjun ZhangFei Gao

Abstract

Sertoli and Leydig cells, the two major somatic cell types in the testis, have different morphologies and functions. Both are essential for gonad development and spermatogenesis. However, whether these cells are derived from the same progenitor cells and the mechanism regulating the differentiation between these two cell types during gonad development remains unclear. A previous study showed that overactivation of Ctnnb1 (cadherin-associated protein, beta 1) in Sertoli cells resulted in Sertoli cell tumors. Surprisingly, in the present study, we found that simultaneous deletion of Wilms' Tumor Gene 1 (Wt1) and overactivation of Ctnnb1 in Sertoli cells led to Leydig cell-like tumor development. Lineage tracing experiments revealed that the Leydig-like tumor cells were derived from Sertoli cells. Further studies confirmed that Wt1 is required for the maintenance of the Sertoli cell lineage and that deletion of Wt1 resulted in the reprogramming of Sertoli cells to Leydig cells. Consistent with this interpretation, overexpression of Wt1 in Leydig cells led to the up-regulation of Sertoli cell-specific gene expression and the down-regulation of steroidogenic gene expression. These results demonstrate that the distinction between Ser...Continue Reading

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Citations

Mar 13, 2016·Seminars in Cell & Developmental Biology·Qing WenYi-Xun Liu
Apr 14, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Hong WangZuping He
Oct 21, 2016·Molecular and Cellular Endocrinology·Haolin ChenBarry R Zirkin
Jan 23, 2016·Biology of Reproduction·Su-Ren Chen, Yi-Xun Liu
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Jan 5, 2021·Frontiers in Cell and Developmental Biology·Martin A EstermannCraig A Smith
May 29, 2021·Frontiers in Cell and Developmental Biology·Bang LiuZuping He
Nov 13, 2020·Physiological Reviews·Yoshitaka NagahamaMasaru Nakamura
Aug 19, 2021·Cell Reports·Yoshifumi MoriTakashi Shinohara
Oct 10, 2021·American Journal of Human Genetics·Eisa MahyariDonald F Conrad

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