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Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients

ABSTRACT: Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients

PROVIDER: PRJNA716050 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14019009.fastq.gz	Fastqsanger.gz
	SRR14019010.fastq.gz	Fastqsanger.gz
	SRR14019011.fastq.gz	Fastqsanger.gz
	SRR14019012.fastq.gz	Fastqsanger.gz

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Epigenome analysis of decidua tissues from unexplained recurrent spontaneous abortion patients and controls with induced abortions

Project description:Genome wide DNA methylation profiling of decidua samples from unexplained recurrent spontaneous abortion patients and controls with induced abortions. The Infinium Human Methylation 850K BeadChip was used to obtain DNA methylation profiles across approximately 853,307 CpGs in decidua samples . Samples included 2 normal pregnant women (non-medical reasons for abortion) and 4 unexplained recurrent spontaneous abortion patients.

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RNA sequencing analysis of decidua tissues from unexplained recurrent spontaneous abortion patients and controls with induced abortions

Project description:Recurrent spontaneous abortion (RSA), defined as the failure of two or more consecutive clinical pregnancies before 20 weeks of gestation, affects approximately 1% of couples attempting to conceive. However, the underlying mechanisms of 50% of cases are unknown. The decidua plays a crucial role during pregnancy, which can provide a delicate balance between immune tolerance and defense to maintain the pregnancy.We performed RNA-seq to identify gene expression alterations in the deciduas of RSA patients and controls. RNA-seq was done using TruSeq Stranded mRNA Library Preparation. Briefly, intact RNA was fragmented, end repaired, adapter ligation and PCR amplified following illumina protocol. Libraries were sequencing by illumins Hiseq 2000. After quality control, sequence data were processed with STAR to generate read alignments with hg19. Raw read counts for annotated genes were obtained with featureCounts with default settings, normalized and analyzed using DEseq2.

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Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients

Project description:We isolated CD14+CD45+ dMΦ from the normal or RSA decidua by flow cytometry, followed by single cell RNA sequencing (scRNA-seq). In total, 23,062 single-cell transcriptomes of macrophage were profiled (12,470 Normal and 10,592 RSA), which were divided into 13 major clusters via T-distributed stochastic neighbor embedding (t-SNE) visualization.

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Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk

Project description:Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.

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