Cell communication and signaling : CCS · 2019
Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Jingjing, Li Jinmei, Xu Wei, Xia Qin, Gu Yunzhao, Song Weixiang, Zhang Xiaoyu, Yang Yang, Wang Wei, Li Hua, Zou Kang
Аннотация
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.
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.