Chronic Chlamydia infection in fallopian tube organoids alters epithelial differentiation and accelerate methylation changes
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PROVIDER: PRJNA421169 | ENA |
REPOSITORIES: ENA
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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
Project description:Chronic Chlamydia trachomatis infection of fallopian tube organoids
| PRJNA422811 | ENA
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
Project description:Characterization of the protein composition of the extracellular matrix (ECM) of normal human Fallopian tube samples.
2021-11-02 | PXD023707 | Pride
Project description:Primary mesenchymal cells from the human fallopian tube infected with Chlamydia trachomatis
| PRJNA430871 | ENA
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
Project description:This study characterizes changes in miRNA signatures in fallopian-tube derived cancer models.
2020-04-14 | GSE126549 | GEO
Project description:Background. Fallopian tube secretory epithelial cells (FTSECs) have been implicated as a cell-of-origin for high-grade serous epithelial ovarian cancer. However, there are relatively few in vitro models of this tissue type available for use in studies of FTSEC biology and malignant transformation. In vitro three-dimensional (3D) cell culture models aim to recreate the architecture and geometry of tissues in vivo and restore the complex network of cell-cell/cell-matrix interactions that occur throughout the surface of the cell membrane. Results. We have established and characterized 3D spheroid culture models of primary FTSECs. FTSEC spheroids contain central cores of hyaline matrix surrounded by mono- or multi-layer epithelial sheets. We found that 3D culturing alters the molecular characteristics of FTSECs compared to 2D cultures of the same cells. Gene expression profiling identified more than a thousand differentially expressed genes between 3D and 2D cultures of the same FTSEC lines. Pathways significantly under-represented in 3D FTSEC cultures were associated with cell cycle progression and DNA replication. This was also reflected in the reduced proliferative indices observed in 3D spheroids stained for the proliferation marker MIB1. Comparisons with gene expression profiles of fresh fallopian tube tissues revealed that 2D FTSEC cultures clustered with follicular phase tubal epithelium, whereas 3D FTSEC cultures clustered with luteal phase samples. Conclusions. This 3D model of fallopian tube secretory epithelial cells will advance our ability to study the underlying biology and etiology of fallopian tube tissues and the pathogenesis of high-grade serous epithelial ovarian cancer. 3 primary FTSEC lines were plated in 2D, or in 3D on polyHEMA coated plates
2013-09-27 | E-GEOD-51220 | biostudies-arrayexpress
Project description:Transcriptomic data of human fallopian tube secretory epithelial cells. Main correspondance: Kate.Lawrenson@cshs.org
2022-06-21 | GSE182510 | GEO