Defective germline reprogramming rewires the spermatogonial transcriptome
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ABSTRACT:
PROVIDER: PRJEB25489 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2380904_1.fastq.gz | Fastqsanger.gz | |||
| ERR2380904_2.fastq.gz | Fastqsanger.gz | |||
| ERR2380905_1.fastq.gz | Fastqsanger.gz | |||
| ERR2380905_2.fastq.gz | Fastqsanger.gz | |||
| ERR2380906_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.
2018-03-09 | E-MTAB-6202 | biostudies-arrayexpress
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:Defective germ line 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.
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Project description:Germline stem cells are unipotent stem cells dedicated to differentiate into gemmates throughout of life. However, spontaneous reprogramming of spermatogonial stem cells (SSCs) in long-term culture indicates the acquirement of pluripotency of germ cells affected by microenvironment.epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and fresh mouse embryonic fibroblast (MEF) feeder are essential for transformation, and addition of 2i further enhanced the pluripotency. Transcriptome analysis revealed that EGF activated RAS signaling pathway and inhibited p38 to initiate transformation, and synergically cooperated with LIF to promote the transformation propensity. The increased efficiency of SSCs spontaneous reprogramming established new avenues for regenerative medicine, animal cloning, and research model for germline fate determination.
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Project description:Multipotent spermatogonial stem cells (mSSCs) derived from SSCs are a potential new source of individualized pluripotent cells in regenerate medicine such as ESCs. We hypothesized that the culture-induced reprogramming of SSCs was mediated by a mechanism different from that of iPS, and was due to up-regulation of specific pluripotency-related genes during cultivation. Through a comparative analysis of expression profile data, we try to find cell reprogramming candidate factors from mouse spermatogonial stem cells. We used microarrays to analyze the gene expression profiles of culture-induced reprogramming converting unipotent spermatogonial stem cells to pluripotent spermatogonial stem cells. Three types of spermatogonial stem cells were mechanically collected according to morphological criteria for RNA extraction and hybridization on Affymetrix microarrays.
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