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Essential Regulation of YAP1 in Fate Determinations of Spermatogonial Stem Cells and Male Fertility by Interacting with RAD21 and Targeting NEDD4 in Humans and Mice 认领 引用 被引量：2
1
作者 Chunyun Li Wei Chen +4 位作者 Yinghong Cui Dong Zhang Qingqing Yuan Xing Yu Zuping He 《Research》 SCIE EI CSCD 2025年第3期556-573,共18页
Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells(SSCs)undergo self-renewal and differentiation into spermatozoa.Molecular mechanisms underlying fate determinations of human SSCs... Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells(SSCs)undergo self-renewal and differentiation into spermatozoa.Molecular mechanisms underlying fate determinations of human SSCs by key genes and signaling pathways remain elusive.Here,we report for the first time that Yes1-associated transcriptional regulator(YAP1)is required for fate determinations of SSCs and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice.YAP1 was mainly located at cell nuclei of human SSCs.YAP1 silencing resulted in the decreases in proliferation and DNA synthesis as well as an enhancement in apoptosis of human SSCs both in vivo and in vitro.RNA sequencing and real-time polymerase chain reaction assays identified NEDD4 as a target of YAP1,and NEDD4 knockdown inhibited the proliferation of human SSCs and increased their apoptosis.Furthermore,YAP1 interacted with RAD21 to regulate NEDD4 transcription in human SSCs.Importantly,YAP1 abnormalities were found to be associated with non-obstructive azoospermia(NOA)as manifested as lower expression level of YAP1 in testicular tissues of NOA patients and YAP1 single-nucleotide variants(SNVs)in 777 NOA patients.Finally,Yap1 germline conditional knockout(cKO)mice assumed mitotic arrest,low sperm count,and motility.Collectively,these results highlight a critical role of YAP1 in determining the fate determinations of human SSCs and male infertility through the YAP1/RAD21/NEDD4 pathway.This study provides new insights into the genetic regulatory mechanisms underlying human spermatogenesis and the pathogenesis of NOA,and it offers new targets for gene therapy of male infertility. 展开更多
关键词 fate determinations YAP signaling pathways spermatogonial stem cells sscs undergo Spermatogonial Stem Cells Male Fertility targeting nedd RAD
The roles and regulation of Yes-associated protein 1 in stem cells 认领 引用 被引量：1
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作者 QING YIN CAIHONG LIU +3 位作者 WENYING JIANG HAIHUI GONG CHUNYUN LI ZUPING HE 《BIOCELL》 SCIE 2023年第1期33-39,共7页
Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of ... Yes-associated protein 1(YAP1)is a downstream effector of the Hippo signaling pathway,and it is involved in tumorigenesis,tissue repair,growth,and development.In this review,the biological roles and the mechanisms of YAP1 in mediating stem cell fate decisions are discussed,including cell proliferation,differentiation,and apoptosis.In general,YAP1 promotes the proliferation and differentiation of stem cells,including embryonic stem cells and adult stem cells.It inhibits apoptosis by binding to the transcription factors,e.g.,transcriptional enhanced associate domain(TEAD),Smad,runt-related transcription factor 1/2,p73,p63,and Erb84,to maintain tissue homeostasis.The translocalization of YAP1 in cellular nuclei and the phosphorylation in the cytoplasm work as important and unusual events for the activation of YAP1.Moreover,YAP1 serves as the crosstalk for the Hippo pathway and other signaling pathways,including the Wnt and Notch pathways.It is highlighted in this review that YAP1 is an essential regulator for stem cells that have significant applications in regenerative medicine and reproductive medicine. 展开更多
关键词 YAP1 Hippo signaling pathway Stem cells Fate determinations
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