Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.

Autor: Wang, Jingjing, Li, Jinmei, Xu, Wei, Xia, Qin, Gu, Yunzhao, Song, Weixiang, Zhang, Xiaoyu, Yang, Yang, Wang, Wei, Li, Hua, Zou, Kang
Předmět:
Zdroj: Cell Communication & Signaling; 5/29/2019, Vol. 17 Issue 1, pN.PAG-N.PAG, 1p
Abstrakt: Background: Androgen plays a pivotal role in spermatogenesis, accompanying a question how androgen acts on germ cells in testis since germ cells lack of androgen receptors (AR). Promyelocytic leukemia zinc-finger (PLZF) is essential for maintenance of undifferentiated spermatogonia population which is terminologically called spermatogonia progenitor cells (SPCs). Aims: We aim to figure out the molecular connections between androgen and fates of PLZF+ SPCs population. Method: Immunohistochemistry was conducted to confirm that postnatal testicular germ cells lacked endogenous AR. Subsequently, total cells were isolated from 5 dpp (day post partum) mouse testes, and dihydrotestosterone (DHT) and/or bicalutamide treatment manifested that Plzf was indirectly regulated by androgen. Then, Sertoli cells were purified to screen downstream targets of AR using ChIP-seq, and gene silence and overexpression were used to attest these interactions in Sertoli cells or SPCs-Sertoli cells co-culture system. Finally, these connections were further verified in vivo using androgen pharmacological deprivation mouse model. Results: Gata2 is identified as a target of AR, and β1-integrin is a target of Wilms' tumor 1 (WT1) in Sertoli cells. Androgen signal negatively regulate β1-integrin on Sertoli cells via Gata2 and WT1, and β1-integrin on Sertoli cells interacts with E-cadherin on SPCs to regulate SPCs fates. Conclusion: Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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