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

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of mono- or symmetric dimethylarginine residues on histones and non-histone substrates and has been demonstrated to play important roles in many biological processes. In the present study, we observed that PRMT5 is abundantly expressed in spermatogonial stem cells (SSCs) and that Prmt5 deletion results in a progressive loss of SSCs and male infertility. The proliferation of Prmt5-deficient SSCs cultured in vitro exhibited abnormal proliferation, cell cycle arrest in G0/G1 phase and a significant increase in apoptosis. Furthermore, PLZF expression was dramatically reduced in Prmt5-deficient SSCs, and the levels of H3K9me2 and H3K27me2 were increased in the proximal promoter region of the Plzf gene in Prmt5-deficient SSCs. Further study revealed that the expression of lysine demethylases (JMJD1A, JMJD1B, JMJD1C, and KDM6B) was significantly reduced in Prmt5-deficient SSCs and that the level of permissive arginine methylation H3R2me2s was significantly decreased at the upstream promoter region of these genes in Prmt5-deficient SSCs. Our results demonstrate that PRMT5 regulates spermatogonial stem cell development by modulating histone H3 lysine modifications.

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In vitro differentiation of spermatogonial stem cells to functional sperm in zebrafish

Reproduction Abstracts ◽

10.1530/repabs.1.p356 ◽

2014 ◽

Author(s):

Noriyoshi Sakai

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells ◽

In Vitro Differentiation

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Homing of mouse spermatogonial stem cells on acellular testis following in vitro transplantation.

10.26226/morressier.5af300b3738ab10027aa9b14 ◽

2018 ◽

Author(s):

Mansoureh Movahedin

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells

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In Vitro Propagation of Human Prepubertal Spermatogonial Stem Cells

JAMA ◽

10.1001/jama.2011.791 ◽

2011 ◽

Vol 305 (23) ◽

pp. 2416 ◽

Cited By ~ 139

Author(s):

Hooman Sadri-Ardekani

Keyword(s):

Stem Cells ◽

In Vitro Propagation ◽

Spermatogonial Stem Cells

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Propagation of bovine spermatogonial stem cells in vitro

Reproduction ◽

10.1530/rep-07-0419 ◽

2008 ◽

Vol 136 (5) ◽

pp. 543-557 ◽

Cited By ~ 90

Author(s):

Pedro M Aponte ◽

Takeshi Soda ◽

Katja J Teerds ◽

S Canan Mizrak ◽

Henk J G van de Kant ◽

...

Keyword(s):

Stem Cells ◽

Growth Factor ◽

Cultured Cells ◽

Somatic Cells ◽

Type A ◽

Spermatogonial Stem Cells ◽

Seminiferous Tubules ◽

Type A Spermatogonia ◽

Stimulation Of

The access to sufficient numbers of spermatogonial stem cells (SSCs) is a prerequisite for the study of their regulation and further biomanipulation. A specialized medium and several growth factors were tested to study thein vitrobehavior of bovine type A spermatogonia, a cell population that includes the SSCs and can be specifically stained for the lectin Dolichos biflorus agglutinin. During short-term culture (2 weeks), colonies appeared, the morphology of which varied with the specific growth factor(s) added. Whenever the stem cell medium was used, round structures reminiscent of sectioned seminiferous tubules appeared in the core of the colonies. Remarkably, these round structures always contained type A spermatogonia. When leukemia inhibitory factor (LIF), epidermal growth factor (EGF), or fibroblast growth factor 2 (FGF2) were added, specific effects on the numbers and arrangement of somatic cells were observed. However, the number of type A spermatogonia was significantly higher in cultures to which glial cell line-derived neurotrophic factor (GDNF) was added and highest when GDNF, LIF, EGF, and FGF2 were all present. The latter suggests that a proper stimulation of the somatic cells is necessary for optimal stimulation of the germ cells in culture. Somatic cells present in the colonies included Sertoli cells, peritubular myoid cells, and a few Leydig cells. A transplantation experiment, using nude mice, showed the presence of SSCs among the cultured cells and in addition strongly suggested a more than 10 000-fold increase in the number of SSCs after 30 days of culture. These results demonstrate that bovine SSC self-renew in our specialized bovine culture system and that this system can be used for the propagation of these cells.

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Enrichment and In Vitro Culture of Spermatogonial Stem Cells from Pre-Pubertal Monkey Testes

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-017-0058-x ◽

2017 ◽

Vol 14 (5) ◽

pp. 557-566 ◽

Cited By ~ 5

Author(s):

Yong-Hee Kim ◽

Hyun-Gu Kang ◽

Bang-Jin Kim ◽

Sang-Eun Jung ◽

Polash C. Karmakar ◽

...

Keyword(s):

Stem Cells ◽

In Vitro Culture ◽

Spermatogonial Stem Cells

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Independent 5' and 3'-end determination of multiple dihydrofolate reductase transcripts

Molecular and Cellular Biology ◽

10.1128/mcb.7.10.3732-3739.1987 ◽

1987 ◽

Vol 7 (10) ◽

pp. 3732-3739

Author(s):

J Y Yen ◽

R E Kellems

Keyword(s):

Dihydrofolate Reductase ◽

Relative Abundance ◽

Transcription Initiation ◽

Promoter Region ◽

Overlapping Genes ◽

Cytoplasmic Rna ◽

Upstream Promoter ◽

Upstream Promoter Region ◽

Polyadenylation Sites

Multiple dihydrofolate reductase (dhfr) mRNAs, differing substantially in abundance, are produced as a result of the utilization of multiple transcription initiation sites and multiple polyadenylation sites. We have shown that dhfr mRNAs initiating from an upstream promoter region utilize the same collection of six polyadenylation sites and generate multiple dhfr mRNAs at the same relative abundance as do the mRNAs initiating from the major transcription promoter region. These results indicate that the 5' and 3' ends of dhfr mRNAs are independently determined. We show that the relative abundance of steady-state dhfr mRNAs was the same in nuclear and cytoplasmic RNA fractions. This finding makes it unlikely that differences in mRNA stability account for differences in the relative abundance of the multiple dhfr mRNAs in the cytoplasm. Our analysis of the dhfr promoter region revealed the existence of stable cytoplasmic polyadenylated transcripts complementary to the first 300 nucleotides of the dhfr transcripts initiating from the upstream promoter region. Therefore, the dhfr locus hosts two divergent and partially overlapping genes which share the same promoter region.

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Long-term health in recipients of transplanted in vitro propagated spermatogonial stem cells

Human Reproduction ◽

10.1093/humrep/dex348 ◽

2017 ◽

Vol 33 (1) ◽

pp. 81-90 ◽

Cited By ~ 15

Author(s):

Callista L Mulder ◽

Lisa A E Catsburg ◽

Yi Zheng ◽

Cindy M de Winter-Korver ◽

Saskia K M van Daalen ◽

...

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells

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Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbit SP-B gene

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2000.278.3.l477 ◽

2000 ◽

Vol 278 (3) ◽

pp. L477-L484 ◽

Cited By ~ 14

Author(s):

Ramgopal Margana ◽

Kiflu Berhane ◽

M. Nurul Alam ◽

Vijayakumar Boggaram

Keyword(s):

Promoter Region ◽

Promoter Activity ◽

Mutational Analysis ◽

Surfactant Protein ◽

Alveolar Type ◽

Deletion Mapping ◽

Clara Cells ◽

Mobility Shift ◽

Upstream Promoter ◽

Upstream Promoter Region

Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. SP-B mRNA is expressed in a cell type-restricted manner in alveolar type II and bronchiolar (Clara) epithelial cells of the lung and is developmentally induced. In NCI-H441 cells, a lung cell line with characteristics of Clara cells, a minimal promoter region comprising −236 to +39 nucleotides supports high-level expression of chloramphenicol acetyltransferase reporter activity. In the present investigation, we characterized the upstream promoter region, −236 to −140 nucleotides, that is essential for promoter activity. Deletion mapping identified two segments, −236 to −170 and −170 to −140 nucleotides, that are important for promoter activity. Mutational analysis and gel mobility shift experiments identified thyroid transcription factor-1, Sp1, and Sp3 as important trans-acting factors that bind to sequences in the upstream promoter region. Our data suggest that SP-B promoter activity is dependent on interactions between factors bound to upstream and downstream regions of the promoter.

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