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Self-renewing Endometrial Epithelial Organoids of the Human Uterus [single-cell RNA-seq data]

ABSTRACT: Self-renewing Endometrial Epithelial Organoids of the Human Uterus [single-cell RNA-seq data]

PROVIDER: PRJNA679950 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13102821.fastq.gz	Fastqsanger.gz
	SRR13102822.fastq.gz	Fastqsanger.gz
	SRR13102823.fastq.gz	Fastqsanger.gz
	SRR13102824.fastq.gz	Fastqsanger.gz
	SRR13102825.fastq.gz	Fastqsanger.gz

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Self-renewing Endometrial Epithelial Organoids of the Human Uterus [bulk RNA-seq data]

Project description:Self-renewing Endometrial Epithelial Organoids of the Human Uterus [bulk RNA-seq data]

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Self-renewing Endometrial Epithelial Organoids of the Human Uterus [bulk RNA-seq data]

Project description:The inner lining of the human uterus, termed the endometrium, is replete with glands that are hypothesized to be important for establishment of pregnancy through interactions with other endometrial cells and the embryo. A three-dimensional culture system was utilized to establish and generate endometrial epithelial organoids from normal human endometrium that display long-term expandability, can be cryopreserved, and are hormone responsive. Here, single cell RNA-seq was used to create a high-resolution gene expression atlas of the endometrial epithelial organoids and to define responsiveness to reproductive hormones.

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Project description:The human endometrium is essential in providing the site for implantation and maintaining the growth and survival of the conceptus. An unreceptive endometrium and disrupted maternal-conceptus interactions can cause infertility due to pregnancy loss or later pregnancy complications. Despite this, the role of uterine glands in first trimester human pregnancy is little understood. An established organoid protocol was used to generate and comprehensively analyze 3-dimensional endometrial epithelial organoid (EEO) cultures from human endometrial biopsies. The derived EEO expand long-term, are genetically stable, and can be cryopreserved. Using endometrium from 2 different donors, EEO were derived and then treated with estrogen (E2) for 2 d or E2 and medroxyprogesterone acetate (MPA) for 6 d. EEO cells were positive for the gland marker, FOXA2, and exhibited appropriate hormonal regulation of steroid hormone receptor expression. Real-time qPCR and bulk RNA-sequencing analysis revealed effects of hormone treatment on gene expression that recapitulated changes in proliferative and secretory phase endometrium. Single-cell RNA sequencing analysis revealed that several different epithelial cell types are present in the EEO whose proportion and gene expression changed with hormone treatment. The EEO model serves as an important platform for studying the physiology and pathology of the human endometrium.

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Progesterone signaling in endometrial epithelial organoids

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Project description:Extensive trauma disrupts endometrial regeneration by diminishing endometrial stem or progenitor cells. Endometrial epithelial organoids (EEOs) are used for endometrial regeneration. However, how EEOs repair injured endometrial tissues and their advantages over bone marrow mesenchymal stem cells (BMSCs) are unclear. This study explored whether EEOs surpass BMSCs to repair injured endometrium and examined whether endometrial restoration involves integrating EEOs into the endometrial tissue of the recipient. Rat EEOs (rEEOs) mimicking the features of the rat endometrium were developed. An endometrial injury rat model was used to compare the effects of rEEOs and rat BMSCs (rBMSCs) on endometrial regeneration and reproductive recovery. Bulk RNA-sequencing analysis was conducted to investigate the capacity of rEEOs for endometrial regeneration and identify discrepancies between rEEOs and rBMSCs. Green fluorescent protein (GFP)-labeled rEEOs or red fluorescent protein-labeled rBMSCs were transplanted to track the transplanted cells in vivo. Fertility recovery in rats transplanted with rEEOs was more comparable to that of normal rats than in rBMSC-treated rats. rEEOs had a high concentration of endometrial epithelial stem or progenitor cells and secreted vascular endothelial growth factor-A to promote endometrial neovascularization. Cells from GFP-labeled rEEOs integrated and differentiated into functional glands within the injured endometrium. Transplanting EEOs restored the morphology and function of severe endometrial injury better than BMSC transplantation. EEO cells repair the endometrium by differentiating into functional glandular epithelial cells. These findings offer preclinical evidence supporting in vitro expansion and transplanting of EEOs as promising approaches to restore fertility in women with insufficient endometrial regeneration.

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