Regulation of long non-coding RNAs and circular RNAs in spermatogonial stem cells

Spermatogonial stem cells (SSCs) are one of the most significant stem cells with the potentials of self-renewal, differentiation, transdifferentiation and dedifferentiation, and thus, they have important applications in reproductive and regenerative medicine. They can transmit the genetic and epigenetic information across generations, which highlights the importance of the correct establishment and maintenance of epigenetic marks. Accurate transcriptional and post-transcriptional regulation is required to support the highly coordinated expression of specific genes for each step of spermatogenesis. Increasing evidence indicates that non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play essential roles in controlling gene expression and fate determination of male germ cells. These ncRNA molecules have distinct characteristics and biological functions, and they independently or cooperatively modulate the proliferation, apoptosis and differentiation of SSCs. In this review, we summarized the features, biological function and fate of mouse and human SSCs, and we compared the characteristics of lncRNAs and circRNAs. We also addressed the roles and mechanisms of lncRNAs and circRNAs in regulating mouse and human SSCs, which would add novel insights into the epigenetic mechanisms underlying mammalian spermatogenesis and provide new approaches to treat male infertility.

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Epigenetic factors in the regulation of prospermatogonia and spermatogonial stem cells

Reproduction ◽

10.1530/rep-14-0679 ◽

2015 ◽

Vol 150 (3) ◽

pp. R77-R91 ◽

Cited By ~ 17

Author(s):

Yen-Tzu Tseng ◽

Hung-Fu Liao ◽

Chih-Yun Yu ◽

Chu-Fan Mo ◽

Shau-Ping Lin

Keyword(s):

Stem Cells ◽

Cell Fate ◽

Cell Formation ◽

Spermatogonial Stem Cells ◽

Epigenetic Landscape ◽

Self Renewal ◽

Male Germline ◽

The Impact

Appropriate regulation of epigenome within cells is crucial for the determination of cell fate and contributes to the lifelong maintenance of tissue homeostasis. Epigenomic re-establishment during embryonic prospermatogonia development and fine-tune of the epigenetic landscape in postnatal spermatogonial stem cells (SSCs) are two key processes required for functional male germ cell formation. Repression of re-activated transposons and male germline-specific epigenome establishment occur in prospermatogonia, whereas modulations of the epigenetic landscape is important for SSC self-renewal and differentiation to maintain the stem cell pool and support long-term sperm production. Here, we describe the impact of epigenome-related regulators and small non-coding RNAs as well as the influence of epigenome modifications that result from extrinsic signaling for controlling the decision between self-renewal, differentiation and survival in mouse prospermatogonia and SSCs. This article provides a review of epigenome-related molecules involved in cell fate determination in male germ cells and discusses the intriguing questions that arise from these studies.

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The Signaling Pathway of Spermatogonial Stem Cells Self-Renewal Induced by Glial Cell Line-Derived Neurotrophic Factor

ACTA BIOPHYSICA SINICA ◽

10.3724/sp.j.1260.2012.10047 ◽

2012 ◽

Vol 28 (1) ◽

pp. 29 ◽

Cited By ~ 1

Author(s):

Haichao LIU ◽

Junming REN ◽

Yingji WU

Keyword(s):

Stem Cells ◽

Cell Line ◽

Signaling Pathway ◽

Glial Cell ◽

Neurotrophic Factor ◽

Spermatogonial Stem Cells ◽

Self Renewal

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Regulation of self-renewal activity of spermatogonial stem cells

Journal of The Society of Japanese Women Scientists ◽

10.5939/sjws.19001 ◽

2019 ◽

Vol 19 (1) ◽

pp. 1-10

Author(s):

Mito Kanatsu-Shinohara

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells ◽

Self Renewal

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Antioxidant or Apoptosis Inhibitor Supplementation in Culture Media Improves Post-Thaw Recovery of Murine Spermatogonial Stem Cells

Antioxidants ◽

10.3390/antiox10050754 ◽

2021 ◽

Vol 10 (5) ◽

pp. 754

Author(s):

Sang-Eun Jung ◽

Hui-Jo Oh ◽

Jin-Seop Ahn ◽

Yong-Hee Kim ◽

Bang-Jin Kim ◽

...

Keyword(s):

Stem Cells ◽

Functional Activity ◽

Culture Media ◽

Quantitative Polymerase Chain Reaction ◽

Spermatogonial Stem Cells ◽

Ros Generation ◽

Apoptosis Assay ◽

Polymerase Chain ◽

Apoptosis Inhibitor

We postulated that supplementation of antioxidant or apoptosis inhibitor in post-thaw culture media of spermatogonial stem cells (SSCs) alleviates reactive oxygen species (ROS) generation and apoptosis. Our aim was to develop an effective culture media for improving post-thaw recovery of SSCs. To determine the efficacy of supplementation with hypotaurine (HTU), α-tocopherol (α-TCP), and Z-DEVD-FMK (ZDF), we assessed the relative proliferation rate and SSC functional activity and performed a ROS generation assay, apoptosis assay, and western blotting for determination of the Bax/Bcl-xL ratio, as well as immunocytochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) for SSC characterization. The relative proliferation rates with HTU 400 μM (133.7 ± 3.2%), α-TCP 400 μM (158.9 ± 3.6%), and ZDF 200 μM (133.1 ± 7.6%) supplementation were higher than that in the DMSO control (100 ± 3.6%). ROS generation was reduced with α-TCP 400 μM (0.8-fold) supplementation in comparison with the control (1.0-fold). Early apoptosis and Bax/Bcl-xL were lower with α-TCP 400 μM (2.4 ± 0.4% and 0.5-fold) and ZDF 200 μM (1.8 ± 0.4% and 0.3-fold) supplementation in comparison with the control (5.3 ± 1.4% and 1.0-fold) with normal characterization and functional activity. Supplementation of post-thaw culture media with α-TCP 400 μM and ZDF 200 μM improved post-thaw recovery of frozen SSCs via protection from ROS generation and apoptosis after cryo-thawing.

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Both Gfrα1a and Gfrα1b Are Involved in the Self-Renewal and Maintenance of Spermatogonial Stem Cells in Medaka

Stem Cells and Development ◽

10.1089/scd.2018.0177 ◽

2018 ◽

Vol 27 (23) ◽

pp. 1658-1670

Author(s):

Yang Zhao ◽

Zhuo Yang ◽

Yuan Wang ◽

Yubing Luo ◽

Fan Da ◽

...

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells ◽

The Self ◽

Self Renewal

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PD08-03 PROFILING OF HUMAN ADULT SPERMATOGONIAL STEM CELLS REVEALS TRANSCRIPTION AND SIGNALING PROGRAMS FOR SELF RENEWAL AND DIFFERENTIATION

The Journal of Urology ◽

10.1016/j.juro.2017.02.530 ◽

2017 ◽

Vol 197 (4S) ◽

Author(s):

Jingtao Guo ◽

Edward J. Grow ◽

Chongil Yi ◽

Douglas T. Carrell ◽

James M. Hotaling ◽

...

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells ◽

Self Renewal ◽

Human Adult

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Expression and functional analyses of ephrin type-A receptor 2 in mouse spermatogonial stem cells†

Biology of Reproduction ◽

10.1093/biolre/ioz156 ◽

2019 ◽

Vol 102 (1) ◽

pp. 220-232 ◽

Cited By ~ 3

Author(s):

Hiroko Morimoto ◽

Mito Kanatsu-Shinohara ◽

Kyle E Orwig ◽

Takashi Shinohara

Keyword(s):

Stem Cells ◽

Cell Sorting ◽

Type A ◽

Spermatogonial Stem Cells ◽

Fibroblast Growth Factor 2 ◽

Self Renewal ◽

Spermatogonial Transplantation ◽

Short Hairpin ◽

Functional Analyses ◽

Magnetic Activated Cell Sorting

Abstract Spermatogonial stem cells (SSCs) undergo continuous self-renewal division in response to self-renewal factors. The present study identified ephrin type-A receptor 2 (EPHA2) on mouse SSCs and showed that supplementation of glial cell-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), which are both SSC self-renewal factors, induced EPHA2 expression in cultured SSCs. Spermatogonial transplantation combined with magnetic-activated cell sorting or fluorescence-activated cell sorting also revealed that EPHA2 was expressed in SSCs. Additionally, ret proto-oncogene (RET) phosphorylation levels decreased following the knockdown (KD) of Epha2 expression via short hairpin ribonucleic acid (RNA). Although the present immunoprecipitation experiments did not reveal an association between RET with EPHA2, RET interacted with FGFR2. The Epha2 KD decreased the proliferation of cultured SSCs and inhibited the binding of cultured SSCs to laminin-coated plates. The Epha2 KD also significantly reduced the colonization of testis cells by spermatogonial transplantation. EPHA2 was also expressed in human GDNF family receptor alpha 1-positive spermatogonia. The present results indicate that SSCs express EPHA2 and suggest that it is a critical modifier of self-renewal signals in SSCs.

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