PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Plzf Expression via Modulation of Lysine Histone Modifications

Dong, Fangfang; Chen, Min; Jiang, Lin; Shen, Zhiming; Ma, Longfei; Han, Chunsheng; Guo, Xudong; Gao, Fei

doi:10.3389/fcell.2021.673258

Cited by 6 publications

(7 citation statements)

References 63 publications

(91 reference statements)

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“…A potential upstream regulator of PLZF is PRMT5. Disruption of the PRMT5 gene results in a dramatic reduction of PLZF gene expression, and subsequent progressive loss of SSCs leading to male infertility ( 50 ). Another transcription factor important for maintenance of SSC self-renewal is FOXO1, which regulates a number of genes that are preferably expressed in SSCs ( 51 ).…”

Section: Regulation Of Sscsmentioning

confidence: 99%

Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration

et al. 2022

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Spermatogonial stem cells (SSCs) are a group of adult stem cells in the testis that serve as the foundation of continuous spermatogenesis and male fertility. SSCs are capable of self-renewal to maintain the stability of the stem cell pool and differentiation to produce mature spermatozoa. Dysfunction of SSCs leads to male infertility. Therefore, dissection of the regulatory network of SSCs is of great significance in understanding the fundamental molecular mechanisms of spermatogonial stem cell function in spermatogenesis and the pathogenesis of male infertility. Furthermore, a better understanding of SSC biology will allow us to culture and differentiate SSCs in vitro, which may provide novel stem cell-based therapy for assisted reproduction. This review summarizes the latest research progress on the regulation of SSCs, and the potential application of SSCs for fertility restoration through in vivo and in vitro spermatogenesis. We anticipate that the knowledge gained will advance the application of SSCs to improve male fertility. Furthermore, in vitro spermatogenesis from SSCs sets the stage for the production of SSCs from induced pluripotent stem cells (iPSCs) and subsequent spermatogenesis.

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Section: Regulation Of Sscsmentioning

confidence: 99%

Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration

et al. 2022

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“…IHC and IF procedures were performed as described previously. 22,23 Antibodies were diluted as follows: MVH (1:500, Abcam, ab13840), MVH (1:200, Abcam, ab27591), PLZF (1:100, R&D AF2944), FOXO1 (1:300, Cell Signaling Technology, 2880S), SOX9 (1:500, Millipore, AB5535), KI67 (1:400, Abcam, ab15580), STRA8 (1:200, Abcam, ab49405), SCP3 (1:200, Abcam, ab97672), and p-AKT (1:200, Cell Signaling Technology, 9271S). Stained IHC sections were examined with a Nikon microscope, and images were captured by a Nikon DS-Ri1 CCD camera.…”

Section: Immunohistochemistry (Ihc) Immunofluorescence (If) and Tunel...mentioning

confidence: 99%

The function of Foxo1 in spermatogonia development is independent of PI3K/PTEN signaling

et al. 2022

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Spermatogenesis is a highly coordinated process that initiates shortly after birth and continues throughout the lifespan of male animals. Foxo1 is a transcription factor and is involved in many biological processes. It has been reported that the inactivation of Foxo1 in gonocytes during the embryonic stage causes the defects of spermatogenesis. In the present study, we found that the inactivation of Foxo1 in spermatogonia after birth also caused germ cell loss and male infertility. We found that the initiation of meiosis was not affected; however, the germ cell development was arrested after meiosis and lack of mature spermatozoa in the cauda epididymis. We also found that the proliferation of Foxo1-deficient spermatogonia stem cells was significantly reduced under in vitro conditions. Further study revealed that inactivation of Pten in postnatal spermatogonia using Stra8-Cre did not affect germ cell development and the subcellular location of FOXO1 in Ptendeficient spermatogonia. This study demonstrated that Foxo1 was involved in the development of spermatogonia after birth and the function of Foxo1 was probably not regulated by PI3K/PTEN signaling.

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“…In addition, endogenous molecules participate in the maintenance of spermatogonial stem cell self-renewal. PLZF [ 18 , 19 ], FOXO1 [ 20 ], CARF [ 21 ], and PRMT5 [ 22 ] play their respective roles in the process of SSC self-renewal, and deletion of either molecule results in the gradual loss of SSC, ultimately leading to infertility. Retinoic acid (RA) is a critical molecule in the stimulation of SSC differentiation [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation

Zhou

Zhang

et al. 2023

Biol Res

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Background Spermatogonial stem cells (SSCs) are critical for sustaining spermatogenesis. Even though several regulators of SSC have been identified in rodents, the regulatory mechanism of SSC in humans has yet to be discovered. Methods To explore the regulatory mechanisms of human SSCs, we analyzed publicly available human testicular single-cell sequencing data and found that Ankyrin repeat and SOCS box protein 9 (ASB9) is highly expressed in SSCs. We examined the expression localization of ASB9 using immunohistochemistry and overexpressed ASB9 in human SSC lines to explore its role in SSC proliferation and apoptosis. Meanwhile, we used immunoprecipitation to find the target protein of ASB9 and verified its functions. In addition, we examined the changes in the distribution of ASB9 in non-obstructive azoospermia (NOA) patients using Western blot and immunofluorescence. Results The results of uniform manifold approximation and projection (UMAP) clustering and pseudotime analysis showed that ASB9 was highly expressed in SSCs, and its expression gradually increased during development. The immunohistochemical and dual-color immunofluorescence results displayed that ASB9 was mainly expressed in nonproliferating SSCs. Overexpression of ASB9 in the SSC line revealed significant inhibition of cell proliferation and increased apoptosis. We predicted the target proteins of ASB9 and verified that hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), but not creatine kinase B-type (CKB), has a direct interaction with ASB9 in human SSC line using protein immunoprecipitation experiments. Subsequently, we re-expressed HIF1AN in ASB9 overexpressing cells and found that HIF1AN reversed the proliferative and apoptotic changes induced by ASB9 overexpression. In addition, we found that ABS9 was significantly downregulated in some NOA patients, implying a correlation between ASB9 dysregulation and impaired spermatogenesis. Conclusion ASB9 is predominantly expressed in human SSCs, it affects the proliferation and apoptotic process of the SSC line through HIF1AN, and its abnormal expression may be associated with NOA.

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PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Plzf Expression via Modulation of Lysine Histone Modifications

Cited by 6 publications

References 63 publications

Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration

Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration

The function of Foxo1 in spermatogonia development is independent of PI3K/PTEN signaling

Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation

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