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

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

scholarly journals Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumour fate

2019 ◽  
Author(s):  
Sina Jostes ◽  
Martin Fellermeyer ◽  
Gina Merges ◽  
Glen Kristiansen ◽  
Daniel Nettersheim ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Somatic Cells ◽  
Germ Cell Tumour ◽  
Testicular Germ Cell ◽  
Chip Sequencing ◽  
Testicular Germ Cell Tumours ◽  
Oct4 Protein ◽  
Cell Type Specific ◽  
Specific Deletion

ABSTRACTEmbryonal carcinomas (ECs) and seminomas are testicular germ cell tumours. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use ChIP-sequencing to report and compare the binding pattern of SOX17 in seminoma-like TCam-2 cells to SOX2 in EC-like 2102EP cells and SOX17 in somatic cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and other SOX family member motifs. SOX17 directly regulatesTFAP2C,PRDM1andPRDM14, thereby maintaining latent pluripotency and supressing somatic differentiation. In contrast, in somatic cells canonical motifs are not bound by SOX17. In sum only 11% of SOX17 binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 protein level and loss of alkaline phosphatase activity. Further, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, predominantly by partnering with OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.

143 DEVELOPMENTAL EFFICIENCY IMPROVEMENTS OF NUCLEAR TRANSFER EMBRYOS BY REPROGRAMMING SOMATIC CELLS USING TESTIS-DERIVED CELL EXTRACTS

2007 ◽  
Vol 19 (1) ◽  
pp. 189
Author(s):  
H.-Y. Choi ◽  
C. Won ◽  
B.-W. Kim ◽  
Y.-J. Kang ◽  
G.-H. Kang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Cell ◽  
Nuclear Transfer ◽  
Somatic Cells ◽  
Male Germ Cell ◽  
Kidney Cells ◽  
Cell Extracts ◽  
Donor Cells ◽  
Porcine Testis

Somatic cell cloning has promise for medical treatment using embryonic stem cells derived from cloned embryos. However, porcine cloning by somatic cell nuclear transfer has been inefficient and, even after birth, cloned pigs are found to carry a variety of abnormalities. Moreover, recent molecular analyses of cloned embryos have revealed abnormal epigenetic modifications. Therefore, the prevention of epigenetic errors is expected to lead to the improvement of the success rate in animal cloning. Reports of recent studies indicate that the direct transformation of one differentiated somatic cell type into another is possible and would be advantageous for producing isogenic replacement cells. Therefore, in this study, we modulated the cell fate of somatic donor cells by introducing cell extracts derived from porcine testis. Several porcine somatic cells, including primary and stabilized porcine fibroblasts or epithelial kidney cells, were treated with streptolysin O (SLO; 230 ng mL-1), which reversibly permeablizes plasma membrane, and incubated for 30 min with testis cell-derived cell extracts (4 mg mL-1). To reseal plasma membranes, cells were placed in DMEM containing 30% FBS and 2 mM CaCl2 for 30 min. After resealing the cell membranes, we incubated the cells for 3 weeks and analyzed the expression of testis-specific genes such as protamine 1, protamine 2, SOX 9, mullerian inhibitory substance (MIS), preproacrosine (ACR), phosphoglycerate kinase 2 (PGK-2), protein C, and c-kit ligand. In the reprogrammed primary porcine fibroblasts or epithelial kidney cells, the porcine testis extracts were able to activate the expression of the porcine testis sertoli cell-specific genes. The male germ cell functions were sustained for more than 10 days after the reprogramming process. Then, in vitro-matured oocytes were enucleated and a single cell (either reprogrammed or intact) was injected directly into cytoplasm of the oocytes. The reconstructed embryos were activated electrically and cultured in vitro for 7 days. The rate of blastocyst formation was significantly higher (P < 0.05; chi-square test) in the reprogrammed nuclear donor cells (27/119; 22.7 � 5.0%) than in the control (intact) cells (11/83; 13.3 � 3.2%). Taken together, our results suggest that testis-derived cell extracts can be successfully used to reprogram fibroblasts to express male germ cell function, thus improving the developmental efficiency of the nuclear transfer embryos.

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.

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
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