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Chronic Chlamydia infection in fallopian tube organoids alters epithelial differentiation and accelerate methylation changes

ABSTRACT: Chronic Chlamydia infection in fallopian tube organoids alters epithelial differentiation and accelerate methylation changes

PROVIDER: PRJNA421169 | ENA |

REPOSITORIES: ENA

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Chronic Chlamydia infection in fallopian tube organoids alters epithelial differentiation and accelerate methylation changes

Project description:Chlamydia trachomatis (Ctr) is able to colonize the human fallopian tube, causing scarring and inflammation, which can lead to infertility. Here we describe a chronic Ctr infection model using human fallopian tube organoids. The defense response of the organoids to infection includes active expulsion of the bacteria from the apical side of the epithelium and compensatory cellular proliferation, clearly demonstrating a role for core mechanisms of epithelial homeostasis in defense against this invading pathogen. During progression in culture for over 9 months, the population of epithelial cells underwent a permanent shift towards a more dedifferentiated state. We identify LIF signaling an essential for regulation of the stemness in the tube and formation of organoids, and report its activation triggered by Ctr . In the long term, chronic Ctr infection leads to changes in the composition of the epithelium, marked by an increase in the proportion of secretory cells, expansion of the CD24+ positive population, upregulation of SPP1 factor, as well as downregulation of inflammatory mediators CD90, CD83, and CCR7. Ctr increases hypermethylation of DNA in polycomb repressed genomic regions - indicator of accelerated molecular aging. This infection model reveals an important link between Ctr and regulation of the host epigenome and suggests that Ctr has a long-term impact on the epithelial interaction with the immune system. These permanent changes in the epithelium may be a contributing factor in the development of tubal pathologies, particularly development of high grade serous ovarian cancer (HGSOC).

2019-01-31 | GSE107712 | GEO

Chronic Chlamydia trachomatis infection of fallopian tube organoids

Project description:Chronic infections of the Fallopian tubes with Chlamydia trachomatis (Ctr) can cause scarring and inflammation and can lead to infertility. Here we describe a model of human fallopian tube organoids for chronic Ctr infection. Interestingly, the normal human cells respond to infection with an active expulsion of the bacteria from the apical side of the epithelium and compensatory cellular proliferation clearly demonstrating a role of epithelial homeostasis in the defense against this infectious agent. Upon progression of the infected culture for over 9 months, the population of epithelial cells underwent a permanent shift towards a less differentiated state. LIF signaling is an essential feature, regulating stemness in the tube and organoid formation, and is activated in response to Ctr. Hallmarks of an organoid infection include a relative increase of secretory cells, expansion of the CD24+ positive population, upregulation of SPP1 factor, as well as downregulation of HOXA4 and HOXA5 homeobox genes. Moreover, Ctr increases hypermethylation of DNA in polycomb repressed genomic regions, an indicator of accelerated molecular aging. This infection model reveals an intriguing link between Ctr and regulation of the host epigenome and suggests that this pathogen has a long-term impact on the interaction of the epithelium with the microenviroment. These permanent changes in the epithelium may be a contributing factor in the development of tubal pathologies, including the development of high grade serous ovarian cancer (HGSOC).

2019-01-31 | GSE108202 | GEO

Chronic Chlamydia trachomatis infection of fallopian tube organoids

Project description:Chronic Chlamydia trachomatis infection of fallopian tube organoids

| PRJNA422811 | ENA

Fallopian tube vs Fimbria

Project description:Fallopian tube vs Fimbria

| PRJNA530990 | ENA

Human iPSC-Derived Fallopian Tube Organoids with BRCA1 Mutation Recapitulate Early Stage Carcinogenesis

Project description:We generate induced pluripotent stem cells (iPSCs) from healthy individuals and young ovarian cancer patients with germline pathogenic BRCA1 mutations. We then differentiate them into a human iPSC-derived fallopian tube organoid model. We recapitulated BRCA1 mutant ovarian carcinogenesis in vitro and showed tumors in vivo. Using the IPSC derived fallopian tube organoid model, we identify a unique transcriptional profile associated with BRCA1 mutation similar to the ovarian cancer profile.

2022-01-24 | GSE190134 | GEO

Profiling of the human Fallopian tube matrisome

Project description:Characterization of the protein composition of the extracellular matrix (ECM) of normal human Fallopian tube samples.

2021-11-02 | PXD023707 | Pride

Fallopian tube vs Fimbria

Project description:Compare luteal and follicular phases of fimbria and ampulla tissue Fallopian tube epithelial cells for gene expression analysis of fimbria and ampulla specimens were obtained using LCM

2020-04-04 | GSE129348 | GEO

Defining Fallopian-tube Derived miRNA Cancer Signatures

Project description:This study characterizes changes in miRNA signatures in fallopian-tube derived cancer models.

2020-04-14 | GSE126549 | GEO

Transcriptomic analysis of human fallopian tube secretory epithelium

Project description:Transcriptomic data of human fallopian tube secretory epithelial cells. Main correspondance: Kate.Lawrenson@cshs.org

2022-06-21 | GSE182510 | GEO

ATAC-seq from fallopian tube (ENCSR565DSD)

Project description:ATAC-seq on human fallopian tube For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf

2022-10-16 | GSE215687 | GEO

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