首页|OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative medicine.Nevertheless,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive.Here,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human SSCs.RNA sequencing identified that NCK2 was a target for 0IP5 in human SSCs,and interestingly,0IP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown assays.NCK2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their apoptosis.Notably,NCK2 knockdown reversed the influence of 0IP5 overexpression on human SSCs.Moreover,0IP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably reduced.Significantly,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 single-nucleotide polymorphism mutations of the OIP5 gene(6.95％),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile men.Collectively,these results implicate that 0IP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with azoospermia.As such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

Yinghong Cui、Wei Chen、Li Du、Zuping He

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The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province

The Research Center of Reproduction and Translational Medicine of Hunan Province,Hunan Normal University School of Medicine,Changsha 410013,Hunan,China

国家自然科学基金国家自然科学基金Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defect in Hunan ProvinceKey Grant of Research and Development in Hunan ProvinceDevelopmental Biology and Breeding湖南省自然科学基金湖南省自然科学基金湖南省自然科学基金Shanghai Key Laboratory ofReproductive Medicine

32170862318728452019SK10122020DK20022022XKQ02052020JJ53802020JJ53832021JJ40365

2024

10.34133/research.0162

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(1)
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