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DNA methylation is predominantly stable in mice offspring born after transplantation of long-term cultured spermatogonial stem cells

ABSTRACT: DNA methylation is predominantly stable in mice offspring born after transplantation of long-term cultured spermatogonial stem cells

PROVIDER: PRJNA880819 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21586200.fastq.gz	Fastqsanger.gz
	SRR21586201.fastq.gz	Fastqsanger.gz
	SRR21586202.fastq.gz	Fastqsanger.gz
	SRR21586203.fastq.gz	Fastqsanger.gz
	SRR21586204.fastq.gz	Fastqsanger.gz

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Similar Datasets

DNA methylation is predominantly stable in mice offspring born after transplantation of long-term cultured spermatogonial stem cells

Project description:Spermatogonial stem cell transplantation (SSCT) is proposed as a fertility therapy for childhood cancer survivors. SSCT starts with cryopreserving a testicular biopsy prior to gonadotoxic treatments such as cancer treatments. When the childhood cancer survivor reaches adulthood and desires biological children, the biopsy is thawed and SSCs are propagated in vitro and subsequently auto-transplanted back into their testis. However, culturing stress during long-term propagation can result in epigenetic changes in the SSCs, such as DNA methylation alterations, and might be inherited by future generations born after SSCT. Therefore, SSCT requires a detailed preclinical epigenetic assessment of the derived offspring before this novel cell therapy is clinically implemented. With this aim, the DNA methylation status of sperm from SSCT-derived offspring, with in vitro propagated SSCs, was investigated in a multigenerational mouse model using reduced-representation bisulfite sequencing. Although there were some methylation differences, they represent less than 0.5% of the total CpGs and methylated regions, in all generations. Unsupervised clustering of all samples showed no distinct grouping based on their pattern of methylation differences. After selecting the few single genes that are significantly altered in multiple generations of SSCT offspring compared to control, we validated the results with quantitative Bisulfite Sanger sequencing and RT-qPCRin various organs. Differential methylation was confirmed only for Tal2, being hypo-methylated in sperm of SSCT offspring and presenting higher gene expression in ovaries of SSCT F1 offspring compared to control F1. We found no major differences in DNA methylation between SSCT-derived offspring and control, both in F1 and F2 sperm. The reassuring outcomes from our study are a prerequisite for promising translation of SSCT to the human situation and gives confidence to proceed to the first clinical trials.

2023-09-01 | GSE213399 | GEO

Sperm DNA methylation is predominantly stable in mice offspring born after transplantation of long-term cultured spermatogonial stem cells.

Project description:BackgroundSpermatogonial stem cell transplantation (SSCT) is proposed as a fertility therapy for childhood cancer survivors. SSCT starts with cryopreserving a testicular biopsy prior to gonadotoxic treatments such as cancer treatments. When the childhood cancer survivor reaches adulthood and desires biological children, the biopsy is thawed and SSCs are propagated in vitro and subsequently auto-transplanted back into their testis. However, culturing stress during long-term propagation can result in epigenetic changes in the SSCs, such as DNA methylation alterations, and might be inherited by future generations born after SSCT. Therefore, SSCT requires a detailed preclinical epigenetic assessment of the derived offspring before this novel cell therapy is clinically implemented. With this aim, the DNA methylation status of sperm from SSCT-derived offspring, with in vitro propagated SSCs, was investigated in a multi-generational mouse model using reduced-representation bisulfite sequencing.ResultsAlthough there were some methylation differences, they represent less than 0.5% of the total CpGs and methylated regions, in all generations. Unsupervised clustering of all samples showed no distinct grouping based on their pattern of methylation differences. After selecting the few single genes that are significantly altered in multiple generations of SSCT offspring compared to control, we validated the results with quantitative Bisulfite Sanger sequencing and RT-qPCRin various organs. Differential methylation was confirmed only for Tal2, being hypomethylated in sperm of SSCT offspring and presenting higher gene expression in ovaries of SSCT F1 offspring compared to control F1.ConclusionsWe found no major differences in DNA methylation between SSCT-derived offspring and control, both in F1 and F2 sperm. The reassuring outcomes from our study are a prerequisite for promising translation of SSCT to the human situation.

| S-EPMC10080964 | biostudies-literature

Gene methylation profiles in offspring born before vs. after maternal bariatric surgery

Project description:Evaluate differences in gene methylation levels between offspring born after maternal bariatric surgery and their siblings born before surgery Offspring born after maternal bariatric surgery (AMS, N=25) vs. offspring born before maternal surgery (BMS, N=25)

2013-05-16 | E-GEOD-44798 | biostudies-arrayexpress

Gene expression profile in offspring born before vs. after maternal bariatric surgery

Project description:Evaluate differences in gene expression levels between offspring born after maternal bariatric surgery and their siblings born before surgery Offspring born after maternal bariatric surgery (AMS, N=23) vs. offspring born before maternal surgery (BMS, N=23)

2013-05-16 | E-GEOD-44407 | biostudies-arrayexpress

Gene methylation profiles in offspring born before vs. after maternal bariatric surgery

Project description:Evaluate differences in gene methylation levels between offspring born after maternal bariatric surgery and their siblings born before surgery

2013-05-16 | GSE44798 | GEO

Gene expression profile in offspring born before vs. after maternal bariatric surgery

Project description:Evaluate differences in gene expression levels between offspring born after maternal bariatric surgery and their siblings born before surgery

2013-05-16 | GSE44407 | GEO

RNA sequencing of hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice

Project description:We demonstrated that the offspring of depressed fathers display reduced resilience to stress and enhanced susceptibility to depression. To explain the observed behavioural phenotypes of depression in offspring produced by depressed fathers, molecular profiling was performed in key brain regions.We examined the hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice by RNA sequencing.

2020-06-28 | GSE133494 | GEO

Induced expression of PD-L1 in spermatogonial stem cells by self-renewal division allows allogeneic offspring production [Sequencing]

Project description:Testis immune privilege is thought to be mediated by somatic cells. However, it is not strong enough to protect allogeneic spermatogonial stem cells (SSCs) transplanted into the seminiferous tubules. Here we report successful production of allogeneic offspring by inducing PD-L1 in SSCs. Activation of self-renewal division induced PD-L1 and B7-H3 expression in cultured SSCs, which produced sperm after allogeneic transplantation. While B7-H3 depletion did not influence colonization, PD-L1 depletion prevented donor-derived spermatogenesis. PD-L1 expression was induced by BCL6B via reactive oxygen species (ROS) generation, suggesting that self-renewal stimulation confers immune privilege by ROS. In contrast, reduced ROS or Mapk14 deficiency downregulated PD-L1 expression. Allogeneic offspring were produced by SSC transplantation into congenitally infertile mice and busulfan-treated wild-type mice. Therefore, SSCs can escape rejection when their self-renewal division is stimulated.

2022-04-11 | GSE129658 | GEO

Induced expression of PD-L1 in spermatogonial stem cells by self-renewal division allows allogeneic offspring production [microarray]

2022-04-11 | GSE129546 | GEO

Maternal hyperglycemia induces alterations in hepatic amino acid, glucose and lipid metabolism of neonatal offspring: Multi-omics insights from a diabetic pig model

Project description:Intrauterine exposure to disturbed maternal glucose metabolism is associated with adverse consequences for the offspring. Hepatic disorders in affected offspring emerge in early development; thus, detection of disease biomarkers at an early stage may elucidate the underlying mechanisms of maternal hyperglycemia-induced metabolic disease and improve timely diagnosis and treatment strategies. To systematically study the molecular consequences of maternal hyperglycemia, we used data independent acquisition (DIA) proteomics and compared the molecular profiles of liver of three days old wild-type piglets born to a transgenic hyperglycemic pig model with those of wild-type piglets born to normoglycemic mothers.

2023-07-10 | PXD040305 | Pride

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