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Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [scRNA-seq]

ABSTRACT: To establish an in vitro endometrial co-culture model, endometrial organoid was co-cultured with endometrial stromal cells in a 3D hydrogel matrix. During this co-culture process, tubular gland development was identified from endometrial organoids, which showed the molecular, morphological and functional properties of human endometrial glands. To further characterize the genetic drive for this phenomenon, we conducted single-cell RNA sequencing analysis at day 1 and day 9 after co-culture.

ORGANISM(S): Homo sapiens

PROVIDER: GSE292827 | GEO | 2025/03/29

REPOSITORIES: GEO

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Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [bulk RNA-seq]

Project description:Little is known about the adenogenesis of human endometrial glands. This study explored endometrial adenogenesis using a novel three-dimensional endometrial assembloid model that integrates human endometrial organoids (EOs) and human endometrial stromal cells (HESCs). The model effectively recapitulated endometrial tubular gland formation, underscoring the critical role of stromal-epithelial interactions. Transcriptomic analyses identified WNT7B as a key intrinsic regulator for EO-derived tubular gland formation, which is extrinsically regulated by TGFβ1-VDR interaction between HESCs and EOs. Estradiol stimulated endometrial gland development via WNT7B downregulation in EOs. This finding was validated in an estradiol-stimulated mouse model and clinical samples from women undergoing in vitro fertilization (IVF) cycles. Uterine-specific WNT7B knockout in mice further confirmed its inhibitory role in endometrial gland development. This study offers insights into endometrial adenogenesis and potential therapeutic targets for related endometrial disorders.

2025-04-08 | GSE294011 | GEO

Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression

Project description:Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression

| PRJNA1247687 | ENA

Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-08 | GSE294012 | GEO

Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [scRNA-seq]

Project description:Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [scRNA-seq]

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Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [bulk RNA-seq]

Project description:Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [bulk RNA-seq]

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RNA-seq of Pluripotent Stem Cell-Derived Endometrial Stromal Fibroblasts in Monolayer Differentiation and in Co-culture with Endometrial Epithelial Organoids

Project description:H9 Pluripotent Stem Cells (PSC) were differentiated to Endometrial Stromal Fibroblasts (PSC-ESF) in monolayer over the course of 12 days. Gene expression was measured at day 0, day 4, day 8, and day 12 of differentiation. At day 12, PSC-ESF were dissociated from monolayer culture for co-culture with endometrial epithelial organoids established from term decidua. Gene expression was also measured after 26 days in co-culture (Cycle 1, vehicle or cAMP/progesterone/estradiol) and after 52 days in co-culture (Cycle 2, vehicle or cAMP/progesterone/estradiol)

2021-05-05 | E-MTAB-10375 | biostudies-arrayexpress

Single-cell RNA Sequencing of Endometrial Assembloid Cultures

Project description:Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterised endometrial assembloids, consisting of gland organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma. We show that acute senescence in glandular epithelium drives secretion of multiple canonical implantation factors, whereas in the stroma it calibrates the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization by inhibiting senescence and mesenchymal-epithelial transition, processes involved in endometrial breakdown and regeneration, respectively. Accelerated decidualization resulted in entrapment of co-cultured human blastocysts in a largely static decidual matrix. By contrast, the presence of senescent decidual cells created a dynamic implantation environment, enabling embryo expansion and attachment, although their persistence led to gradual disintegration of assembloids. Together, our findings demonstrate that senescence controls endometrial fate decisions at implantation and highlight how endometrial assembloids may accelerate the discovery of new treatments to prevent reproductive failure.

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Endometrial profile of low-dose estradiol and tamoxifen combination therapy

2009-02-03 | GSE14518 | GEO

Endometrial profile of low-dose estradiol and tamoxifen combination therapy

Project description:Combination therapy with estrogen and a selective estrogen receptor modulator (SERM) is a promising approach to safely alleviate important side effects related to estrogen deficiency in women at high risk for breast cancer. Data related to endometrial safety of estrogen+SERM co-therapies are limited, however. The primary goal of this study was to evaluate the endometrial profile of low-dose E2 and Tam alone and in combination. In this study 16 postmenopausal female cynomolgus macaques were randomized to receive placebo, low-dose micronized estradiol (E2, 0.25 mg/1800 kcal), the SERM tamoxifen (Tam, 20 mg/1800 kcal), or E2+Tam in a parallel-arm design. Endometrial samples were collected after 4 months of treatment and used for microarray analysis.

2010-05-06 | E-GEOD-14518 | biostudies-arrayexpress

Molecular interactions at the bovine embryo–endometrial epithelium interface

Project description:We aimed to interrogate the embryo–maternal interface for embryo-induced changes in the global transcriptome of bovine endometrial epithelial cells (bEECs). In vitro-produced day-5.5 morulae were cultured in juxtacrine apposition (Contact+) with bEECs, or in transwells (Contact⎼), for 48 h. A group of bEECs cultured in the absence of embryos (Control bEEC) was also included. After co-culture, bEECs were recovered for transcriptome analysis.

2020-08-06 | GSE151868 | GEO

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