MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins

Chen, Jian; Cai, Tao; Zheng, Changcheng; Lin, Xiwen; Wang, Guojun; Liao, Shanhui; Wang, Xiuxia; Gan, Haiyun; Zhang, Daoqin; Hu, Xinning; Wang, Si; Li, Zhen; Feng, Yujun; Yang, Fuquan; Han, Chunsheng

doi:10.1093/nar/gkw1287

Cited by 78 publications

(105 citation statements)

References 57 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR-202-5p is a germ plasm unique miRNA that is abundantly enriched in the gonads of some mammals and lower vertebrates. In mouse, miR-202-5p is specifically expressed in the Sertoli cells of embryonic gonads [11] and in spermatogonial stem cells (SSCs) in the testis [12]. In human testis, miR-202-5p is a germ cell-dependent expressing miRNA in Sertoli cells [13], indicating its role in spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2

Ding¹,

Jin²,

Wang

et al. 2020

Cells

View full text Add to dashboard Cite

MicroRNAs play key roles during ovary development, with emerging evidence suggesting that miR-202-5p is specifically expressed in female animal gonads. Granulosa cells (GCs) are somatic cells that are closely related to the development of female gametes in mammalian ovaries. However, the biological roles of miR-202-5p in GCs remain unknown. Here, we show that miR-202-5p is specifically expressed in GCs and accumulates in extracellular vesicles (EVs) from large growth follicles in goat ovaries. In vitro assays showed that miR-202-5p induced apoptosis and suppressed the proliferation of goat GCs. We further revealed that miR-202-5p is a functional miRNA that targets the transforming growth factor-beta type II receptor (TGFβR2). MiR-202-5p attenuated TGF-β/SMAD signaling through the degradation of TGFβR2 at both the mRNA and protein level, decreasing p-SMAD3 levels in GCs. Moreover, we verified that steroidogenic factor 1 (SF1) is a transcriptional factor that binds to the promoters of miR-202 and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) through luciferase reporter and chromatin immunoprecipitation (ChIP) assays. That contributed to positive correlation between miR-202-5p and CYP19A1 expression and estradiol (E2) release. Furthermore, SF1 repressed TGFβR2 and p-SMAD3 levels in GCs through the transactivation of miR-202-5p. Taken together, these results suggest a mechanism by which miR-202-5p regulates canonical TGF-β/SMAD signaling through targeting TGFβR2 in GCs. This provides insight into the transcriptional regulation of miR-202 and CYP19A1 during goat ovarian follicular development.

show abstract

Section: Introductionmentioning

confidence: 99%

Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2

Ding¹,

Jin²,

Wang

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…In mice, miR-202-5p is the predominant miRNA mature form expressed during testis differentiation and is expressed in somatic sertoli cells but not in germ cells [ 34 ]. In the adult mouse testis, miR-202-5p is enriched in sertoli cells, but both miR-202-5p and -3p mature forms are expressed in germ cells at similar levels [ 35 ]. Notably, knock-out (KO) of mir-202 in the mouse induces premature differentiation of spermatogonial stem cells and reduces stem cells activity, indicating that miR-202 is a key regulator of spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

MiR-202 controls female fecundity by regulating medaka oogenesis

et al. 2018

View full text Add to dashboard Cite

Female gamete production relies on coordinated molecular and cellular processes that occur in the ovary throughout oogenesis. In fish, as in other vertebrates, these processes have been extensively studied both in terms of endocrine/paracrine regulation and protein expression and activity. The role of small non-coding RNAs in the regulation of animal reproduction remains however largely unknown and poorly investigated, despite a growing interest for the importance of miRNAs in a wide variety of biological processes. Here, we analyzed the role of miR-202, a miRNA predominantly expressed in male and female gonads in several vertebrate species. We studied its expression in the medaka ovary and generated a mutant line (using CRISPR/Cas9 genome editing) to determine its importance for reproductive success with special interest for egg production. Our results show that miR-202-5p is the most abundant mature form of the miRNA and that it is expressed in granulosa cells and in the unfertilized egg. The knock out (KO) of mir-202 gene resulted in a strong phenotype both in terms of number and quality of eggs produced. Mutant females exhibited either no egg production or produced a dramatically reduced number of eggs that could not be fertilized, ultimately leading to no reproductive success. We quantified the size distribution of the oocytes in the ovary of KO females and performed a large-scale transcriptomic analysis approach to identified dysregulated molecular pathways. Together, cellular and molecular analyses indicate that the lack of miR-202 impairs the early steps of oogenesis/folliculogenesis and decreases the number of large (i.e. vitellogenic) follicles, ultimately leading to dramatically reduced female fecundity. This study sheds new light on the regulatory mechanisms that control the early steps of follicular development, including possible targets of miR-202-5p, and provides the first in vivo functional evidence that a gonad-predominant microRNA may have a major role in female reproduction.

show abstract

“…Several studies reported the global expression of miRNAs in the murine testis (Buchold et al, ; Hayashi et al, ; Jung et al, ; Ro, Park, Sanders, McCarrey, & Yan, ; Yan et al, ), but few examined miRNA abundance in specific testicular germ cell populations nor identified the functional importance of individual miRNAs during SSC homeostasis. Previous studies suggested that miR‐199a‐3p (Niu et al, ), miR‐106a (He et al, ), miR‐221 (Yang et al, ), and miR‐202 (Chen et al, ) play significant roles in SSCs. In this study, we showed that miR‐100 is predominantly expressed in undifferentiated mouse spermatogonia, particularly SSCs.…”

Section: Discussionmentioning

confidence: 99%

miR‐100 promotes the proliferation of spermatogonial stem cells via regulating Stat3

Huang

et al. 2017

Molecular Reproduction Devel

View full text Add to dashboard Cite

Micro RNAs play important roles during mammalian spermatogenesis, but the function(s) of specific miRNAs remain largely unknown. Here, we report that miR-100 is predominantly expressed in undifferentiated murine spermatogonia, including spermatogonial stem cells (SSCs). We utilized a miRNA mimic and inhibitor to knock down and overexpress miR-100 in cultured SSCs, respectively, finding that the miR-100 promotes the proliferation of SSCs in vitro. Furthermore, signals promoting SSC maintenance induced, whereas retinoic acid repressed, expression of miR-100. Stat3 expression was modulated by miR-100, with increased transcript and protein abundance in the presence of the miR-100 inhibitor versus reduced protein levels following miR-100 overexpression. Stat3 silencing also mimicked the reduced SSC proliferation phenotype associated with elevated miR-100 levels. Importantly, Stat3 silencing rescued the anti-proliferation capacity of miR-100 inhibitor on cultured SSCs. Given that the Stat3 3' untranslated region was not repressed by pre-miR-100 in a standard luciferase reporter assay, we suggest that miR-100 promotes SSC proliferation by indirect regulation of Stat3.

show abstract

MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins

Cited by 78 publications

References 57 publications

Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2

Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2

MiR-202 controls female fecundity by regulating medaka oogenesis

miR‐100 promotes the proliferation of spermatogonial stem cells via regulating Stat3

Contact Info

Product

Resources

About