scholarly journals CDK2 kinase activity is a regulator of male germ cell fate

Development ◽  
2019 ◽  
Vol 146 (21) ◽  
pp. dev180273 ◽  
Author(s):  
Priti Singh ◽  
Ravi K. Patel ◽  
Nathan Palmer ◽  
Jennifer K. Grenier ◽  
Darius Paduch ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Kinase Activity ◽  
Male Germ Cell

scholarly journals CDK2 kinase activity is a regulator of male germ cell fate

2019 ◽  
Author(s):  
Priti Singh ◽  
Ravi K. Patel ◽  
Nathan Palmer ◽  
Jennifer K. Grenier ◽  
Darius Paduch ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Kinase Activity ◽  
Phosphorylation Site ◽  
Male Germ Cell ◽  
Cyclin Dependent Kinase ◽  
Rna Seq ◽  
Temporal Regulation ◽  
Juvenile Males

ABSTRACTThe ability of men to remain fertile throughout their lives depends upon establishment of a spermatogonial stem cell (SSC) pool from gonocyte progenitors, and also maintaining the proper balance between SSC renewal and spermatogenic differentiation throughout life. Depletion of SSCs causes infertility with a Sertoli Cell Only Syndrome (SCOS) phenotype. We previously created a mouse strain in which an inhibitory phosphorylation site (Tyr15) of Cyclin-dependent kinase 2 (Cdk2) was altered. Juvenile males homozygous for this allele (Cdk2Y15S) initiate the first round of spermatogenesis, which originates from prospermatogonia, but meiocytes arrest due to chromosomal defects resembling those in Cdk2-/- mice. Subsequent waves of spermatogonial differentiation and meiosis were largely absent, leading to an SCOS-like phenotype. Here, we demonstrate that Cdk2Y15S/Y15S mice possess mitotically active GFRa1+ SSC-like cells, but they are impaired in their ability to differentiate. Marker analysis and single cell RNA-seq revealed defective differentiation of gonocytes into SSCs. Biochemical and genetic data demonstrated that Cdk2Y15S is a gain-of-function allele causing deregulated kinase activity, and its phenotypic effects could be reversed by mutating the Thr160 positive regulatory site in cis. These results demonstrate that precise temporal regulation of CDK2 activity in male germ cell development and in the cell cycle is critical for long-term spermatogenic homeostasis.

Porcine nuclear transfer using somatic donor cells altered to express male germ cell function

2009 ◽  
Vol 21 (7) ◽  
pp. 882 ◽  
Author(s):  
Sangho Roh ◽  
Hye-Yeon Choi ◽  
Sang Kyu Park ◽  
Cheolhee Won ◽  
Bong-Woo Kim ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Nuclear Transfer ◽  
Cell Function ◽  
Control Cell ◽  
Donor Cell ◽  
Male Germ Cell ◽  
Cell Group ◽  
Cell Extracts

Recent studies reported that the direct transformation of one differentiated somatic cell type into another is possible. In the present study, we were able to modulate the cell fate of somatic cells to take on male germ cell function by introducing cell extracts derived from porcine testis tissue. Fibroblasts were treated with streptolysin O, which reversibly permeabilises the plasma membrane, and incubated with testis extracts. Our results showed that the testis extracts (TE) could activate expression of male germ cell-specific genes, implying that TE can provide regulatory components required for altering the cell fate of fibroblasts. Male germ cell function was sustained for more than 10 days after the introduction of TE. In addition, a single TE-treated cell was injected directly into the cytoplasm of in vitro-matured porcine oocytes. The rate of blastocyst formation was significantly higher in the TE-treated nuclear donor cell group than in the control cell group. The expression level of Nanog, Sox9 and Eomes was drastically increased when altered cells were used as donor nuclei. Our results suggest that TE can be used to alter the cell fate of fibroblasts to express male germ cell function and improve the developmental efficiency of the nuclear transfer porcine embryos.

scholarly journals FGF9 Suppresses Meiosis and Promotes Male Germ Cell Fate in Mice

2010 ◽  
Vol 19 (3) ◽  
pp. 440-449 ◽  
Author(s):  
Josephine Bowles ◽  
Chun-Wei Feng ◽  
Cassy Spiller ◽  
Tara-Lynne Davidson ◽  
Andrew Jackson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Male Germ Cell

243 REPROGRAMMING OF FIBROBLASTS TO EXPRESS MALE GERM CELL OR MAST CELL FUNCTIONS USING TESTIS OR MAST CELL-DERIVED CELL EXTRACTS

2006 ◽  
Vol 18 (2) ◽  
pp. 229
Author(s):  
H.-Y. Choi ◽  
B.-W. Kim ◽  
E.-R. Lee ◽  
S. Roh ◽  
S.-G. Cho
Keyword(s):  
Mast Cell ◽  
Germ Cell ◽  
Cell Fate ◽  
Sertoli Cell ◽  
Male Germ Cell ◽  
Nuclear Transplantation ◽  
Cell Type ◽  
Cell Functions ◽  
Cell Extracts ◽  
Porcine Testis

The concept of epigenetic reprogramming of a somatic nucleus was supported by the birth of cloned animals and the derivation of embryonic stem cells after nuclear transplantation into oocytes. Moreover, recent studies reported that the direct transformation of one differentiated somatic cell type into another is possible and would be advantageous for producing isogenic replacement cells. In this study, we were able to modulate the cell fate of fibroblasts by introducing cell extracts derived from a mast cell line, RBL-2H3. NIH-3T3 cells were treated with streptolysin O (SLO; 230 ng/mL), which reversibly permeablizes plasma membrane, and incubated for 30 min with the mast cell- derived cell extracts (4 mg/mL). After resealing the membrane of the cells, we incubated the cells for 3 weeks and then analyzed them for the expression of mast cell-specific genes such as MAFA (mast cell function-associated antigen) and FceRI (high-affinity IgE receptor). Our results showed that the cell extracts can activate the expression of mast cell-specific genes, implying that cell extracts can provide regulatory components required for reprogramming the cell fate to initiate a transcriptional program specific for the cell type. Moreover, mast cell-specific degranulation and cell morphology changes were observed in cultured mouse fibroblasts. We could detect mast cell-specific functions even after 15 days of incubation. Next, to induce porcine fibroblasts to take on testis sertoli cell-specific properties, we reversibly permeablized porcine primary fibroblasts with SLO (230 ng/mL) and incubated the cells with porcine testis extracts (4 mg/mL). As expected, in the reprogrammed primary porcine fibroblasts, the porcine testis extracts activated the expression of porcine testis sertoli cell-specific genes including protamine 1 and 2, SOX9, MIS (mullerian inhibitory substance), preproacrosine (ACR), phosphoglycerate kinase-2 (PGK-2), protein C, and c-kit ligand. The male germ cell functions were sustained for more than 10 days after the reprogramming process. Taken together, our data suggest that testis- or mast cell-derived cell extracts can reprogram fibroblasts to express male germ cell or mast cell functions, respectively, supporting the concept that cell extracts can reprogram the genome activity to activate cell-specific gene expression. This work was supported by ARPC (Grant no. 204117-03-1-HD110) in Korea, and by Biogreen 21 program (Grant no. 20050401034658).

scholarly journals Cell-fate transition and determination analysis of mouse male germ cells throughout development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiexiang Zhao ◽  
Ping Lu ◽  
Cong Wan ◽  
Yaping Huang ◽  
Manman Cui ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Transitional Cell ◽  
Critical Time ◽  
Mitotic Arrest ◽  
Cell Development ◽  
Male Germ Cell ◽  
Male Germ Cells ◽  
Germ Cell Development

AbstractMammalian male germ cell development is a stepwise cell-fate transition process; however, the full-term developmental profile of male germ cells remains undefined. Here, by interrogating the high-precision transcriptome atlas of 11,598 cells covering 28 critical time-points, we demonstrate that cell-fate transition from mitotic to post-mitotic primordial germ cells is accompanied by transcriptome-scale reconfiguration and a transitional cell state. Notch signaling pathway is essential for initiating mitotic arrest and the maintenance of male germ cells’ identities. Ablation of HELQ induces developmental arrest and abnormal transcriptome reprogramming of male germ cells, indicating the importance of cell cycle regulation for proper cell-fate transition. Finally, systematic human-mouse comparison reveals potential regulators whose deficiency contributed to human male infertility via mitotic arrest regulation. Collectively, our study provides an accurate and comprehensive transcriptome atlas of the male germline cycle and allows for an in-depth understanding of the cell-fate transition and determination underlying male germ cell development.

scholarly journals Nodal/activin signaling promotes male germ cell fate and suppresses female programming in somatic cells

Development ◽  
2012 ◽  
Vol 140 (2) ◽  
pp. 291-300 ◽  
Author(s):  
Q. Wu ◽  
K. Kanata ◽  
R. Saba ◽  
C.-X. Deng ◽  
H. Hamada ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Somatic Cells ◽  
Male Germ Cell ◽  
Activin Signaling
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