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Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background

ABSTRACT: Transcriptional profiling of E14.5 XY germ cells (marked with Oct4-EGFP transgene) from two strain backgrounds (C57BL/6J and 129S1/SvImJ) that differ in their susceptibility to testicular teratomas.

ORGANISM(S): Mus musculus

PROVIDER: GSE24340 | GEO | 2010/12/22

SECONDARY ACCESSION(S): PRJNA132899

REPOSITORIES: GEO

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Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background

Project description:Transcriptional profiling of E14.5 XY germ cells (marked with Oct4-EGFP transgene) from two strain backgrounds (C57BL/6J and 129S1/SvImJ) that differ in their susceptibility to testicular teratomas. Two condition experiment. For each sample, Oct4-EGFP+ germ cells from all XY embyos within a litter were pooled. For the C57BL/6J background, n=3 pooled biological replicates were profiled, and n=2 replicates were obtained and profiled for 129S1/SvImJ.

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Strain differences in e11.5 XY gonad transcriptome suggest a mechanism for the sensitivity of C57BL/6J to sex reversal

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Transcription profiling of mouse strain differences in e11.5 XY gonad transcriptome suggest a mechanism for the sensitivity of C57BL/6J to sex reversal

Project description:Transcriptional profiling of individual mouse embryonic (e11.5) XY gonads comparing inbred strains that are sensitive (C57BL/6J) and resistant (129S1/SvImJ) to XY sex reversal, and their reciprocal F1 hybrids. Experiment Overall Design: Two-color Agilent microarray profiles of 20 individual pairs of e11.5 XY gonads, including 5- C57BL/6J, 5- 129S1/SvImJ, 5- (B6x129S1)F1, and 5- (129S1xB6)F1 samples. Within each strain, samples were collected from multiple litters to account for potential litter biases. All samples were processed following the same protocol.

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Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background.

Project description:Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1(Ter/Ter) mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1(Ter/Ter) mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1(Ter/Ter); Bax(-/-) double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1(Ter/Ter) germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27(Kip1) and p21(Cip)(1). P27(Kip1) and P21(Cip1) protein are both significantly decreased in Dnd1(Ter/Ter) germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility.

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Fine Time-Course Expression Analysis of Mammalian Sex Determination in 129S1/SvImJ and C57BL/6J XX and XY mice

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