Defective germline reprogramming rewires the spermatogonial transcriptome
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ABSTRACT:
PROVIDER: PRJEB23111 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2178240_1.fastq.gz | Fastqsanger.gz | |||
| ERR2178240_2.fastq.gz | Fastqsanger.gz | |||
| ERR2178241_1.fastq.gz | Fastqsanger.gz | |||
| ERR2178241_2.fastq.gz | Fastqsanger.gz | |||
| ERR2178242_1.fastq.gz | Fastqsanger.gz |
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Project description:Defective germline reprogramming in Miwi2- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises due to defective germline reprogramming rather than a function for the respective factors within spermatogonia. In both Miwi2-/- and Dnmt3l-/- spermatogonia the intracisternal-A particle (IAP) family of endogenous retroviruses is de-repressed, but in contrast to meiotic cells DNA damage is not observed. Instead we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring host genes. In summary, defective reprogramming deregulates the spermatogonial transcriptome that may underlie spermatogonial dysfunction.
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Project description:Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia. In both Miwi2-/- and Dnmt3l-/- spermatogonia, the intracisternal-A particle (IAP) family of endogenous retroviruses is derepressed, but, in contrast to meiotic cells, DNA damage is not observed. Instead, we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring genes. Finally, spermatogonial numbers, proliferation and differentiation are altered in Miwi2-/- and Dnmt3l-/- mice. In summary, defective reprogramming deregulates the spermatogonial transcriptome and may underlie spermatogonial dysfunction.
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Project description:We analyzed transcriptome profiles of postnatal germ cells and demonstrated that DNMT3L is important for spermatogonial stem/progenitor cell development Examination of wild-type and Dnmt3l knockout smaples in postnatal male germ cells
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Project description:Defective germline reprogramming rewires the spermatogonial transcriptome
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Project description:A bioenergetic balance between glycolysis and mitochondrial respiration is particularly important for stem cell fate specification. It however remains to be determined whether undifferentiated spermatogonia switch their preference of bioenergy production during differentiation. In this study, we found that ATP generation in spermatogonia was gradually increased upon retinoic acid-induced differentiation. To accommodate this elevated energy demand, retinoic acid signaling concomitantly switched ATP production in spermatogonia from glycolysis to mitochondrial respiration, accompanied by increased levels of reactive oxygen species. In addition, inhibition of glucose conversion to glucose-6-phosphate or pentose phosphate pathway blocked the formation of c-Kit+ differentiating germ cells, suggesting that metabolites produced from glycolysis are required for spermatogonial differentiation. We further demonstrated that the expression levels of several metabolic regulators and enzymes were significantly altered upon retinoic acid-induced differentiation by both RNA-seq analyses and quantitative proteomics. Taken together, our data unveil a critically regulated bioenergetic balance between glycolysis and mitochondrial respiration which is required for spermatogonial proliferation and differentiation.
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