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Transcriptomic responses to hypoxia in endometrial stromal fibroblasts and decidual stromal cells

ABSTRACT: Transcriptomic responses to hypoxia in endometrial stromal fibroblasts and decidual stromal cells

PROVIDER: PRJNA437464 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6819100.fastq.gz	Fastqsanger.gz
	SRR6819110.fastq.gz	Fastqsanger.gz
	SRR6819120.fastq.gz	Fastqsanger.gz
	SRR6819130.fastq.gz	Fastqsanger.gz
	SRR6819140.fastq.gz	Fastqsanger.gz

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Transcriptomic responses to hypoxia in endometrial stromal fibroblasts and decidual stromal cells

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Project description:Implantation is dependent on synchronized interactions between the conceptus and surrounding decidual cells but the involvement of clock genes in this process is not well understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK and BMAL1 and repressors encoded by PER and CRY genes. Here we show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Downregulation was preceded by reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter and occurred between 12 - 24 h after exposure to a deciduogenic stimulus. RNA sequencing revealed that premature inhibition of PER2 by siRNA knockdown leads to a grossly disorganised decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators amongst the 1,121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure. Thus, PER2 synchronizes mitotic expansion of HESCs with a periodic decidual gene expression; uncoupling of these events may cause persistent pregnancy failure. Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-PER2 were generated by deep sequencing, in triplicate using Illumina

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Comparative transcriptomics of endometrial stromal fibroblasts

Project description:Comparative transcriptomics of endometrial stromal fibroblasts

| PRJNA280591 | ENA

PER2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells

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Preimplantation Factor Effect on Endometrial and Decidual Cells

Project description:Embryos secrete preimplantation factor (PIF), a peptide present in maternal circulation during viable pregnancy. We compared downstream synthetic PIF effect on gene expression in non-pregnant Human Endometrial Stromal Cell (HESC) and First Trimester Decidual cell (FTDC) culture to mimic the maternal intrauterine environment during embryo implantation and trophoblast invasion.

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Reconstruction of the decidual pathway in human endometrial cells using single-cell RNA-Seq

Project description:The fate of the human endometrium is determined during the mid-luteal window of implantation, coinciding with differentiation of endometrial stromal cells (EnSCs) into specialized decidual cells. Upon embryo implantation, differentiating EnSCs transform the endometrium into the decidua of pregnancy; whereas falling progesterone levels in the absence of pregnancy lead to tissue breakdown and menstruation. We used single-cell RNA sequencing to map the transcriptomic changes in primary EnSCs along a decidual time-course and in response to withdrawal of differentiation signals. We demonstrate that decidual transformation starts with a precipitous transcriptional response, which is followed by synchronous transition of EnSCs through intermediate states before emerging as divergent subpopulations, representing decidual cells and senescent decidual cells. Single-cell analysis of timed luteal phase biopsies identified multiple endometrial epithelial subpopulations and immune cells, most prominently uterine NK cells. In the stroma, transition from receptive to post-receptive endometrial state was marked by progression of EnSCs along diverging transcriptional trajectories, involving genes with conserved branching dynamics in vivo and in vitro. Our findings indicate that specification of EnSCs into distinct decidual subpopulations underpins endometrial fate decisions during the window of implantation.

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