Single cell RNA sequencing of normal endometrial derived organoids uncovers novel cell type markers for prognostication
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ABSTRACT:
PROVIDER: EGAS00001004466 | EGA |
REPOSITORIES: EGA
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Project description:Endometrial carcinoma, the most common gynecologic cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. We performed single cell sequencing on endometrial and ovarian tumours, and on organoids both treated with DBZ and normal and found both secretory-like and ciliated-like tumour cells.
| EGAD00001006280 | EGA
Project description:Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced by menstrual cycle hormones estrogen (E2; proliferative phase) progesterone (P4; secretory phase) and estrogen plus progesterone (E2P4; the receptive phase). EV sized particles were isolated by differential centrifugation and size exclusion chromatography. Nanoparticle tracking analysis was used to examine the different concentration and size of particles and EV proteomic analysis per-formed using shotgun label-free mass spectrometry. Our results showed that although endome-trial derived EVs were secreted in numbers independent of hormonal stimulation, EVs sizes were statistically modified by it. Proteomics analysis showed that hormone treatment changes affect the endometrial EVs proteome, with proteins enhanced within the EV E2P4 group shown to be in-volved in different processes such as embryo implantation, endometrial receptivity, and embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs.
2023-02-13 | PXD039764 | Pride
Project description:In this study, we sought to understand the effects of excess adipose on the benign endometrium. We used a physiologic in vitro coculture system consisting of multicellular organoids of the benign human endometrium and adipose spheroids in the presence of estradiol, progesterone, and testosterone to mimic the menstrual cycle. Gene expression analysis of endometrial organoids under high adiposity conditions revealed downregulation of genes normally expressed in secretory endometrium, suggestive of an altered progesterone response. Genes associated with ion homeostasis and detoxification of reactive oxygen species were also downregulated, including the metallothionein (MT) family of genes. We demonstrated that MT gene expression in endometrial organoids was regulated by progesterone specifically in the epithelial cells, and that progesterone receptor is recruited to the promoters of MT genes in endometrial epithelial cells. We illustrated the impact of MT dysregulation by silencing MT genes in endometrial epithelial cells, resulting in increased DNA damage. Our results reveal that exposing the endometrium to high adiposity can compromise the protective effects of progesterone, dysregulate MT genes in the endometrial epithelium, and leave the endometrium vulnerable to ROS-induced DNA damage.
2024-04-19 | GSE240926 | GEO
Project description:Impaired endometrial receptivity is one of the major causes of recurrent implantation failure (RIF), and the underlying molecular mechanism has not been fully elucidated. We demonstrated that Chromodomain Y like (CDYL) was highly expressed in the endometrium at mid-secretory phase during the normal menstrual cycles. However, the expression of CDYL was down-regulated in the endometrial tissues obtained from women with RIF, consistently with the protein level of LIF, which is the marker of endometrial receptivity. Knockdown of CDYL significantly decreased the cell migration of human endometrial Ishikawa cells and primary endometrial cells. Genomic analyses revealed that CDYL gene silencing resulted in decreased expression of many genes associated with cytoskeleton and migration regulation.
2020-09-28 | GSE141239 | GEO
Project description:Transcriptional profiling of rat EAC - comparison of non-/pre-malignant endometrium with endometrial tumors Endometrial cancer develops from the endometrium of the uterus and is the most common pelvic malignancy diagnosed in women in the western countries. Similar to all cancer diseases, endometrial cancer is a genetic disorder that results from complex patterns of genetic and epigenetic alterations involved in the malignant transformation. The genetic heterogeneity inherent in the human population, differences in the environment and life styles poses enormous difficulties when analyzing the complex patterns of genetic alterations contributing to cancer etiology. Inbred animal models constitute unique experimental genetic tools as the genetic heterogeneity and the influence of environmental factors can be readily reduced. The BDII/Han rat model is unique for spontaneous hormonal carcinogenesis since more than 90% of the female virgins spontaneously develop endometrial cancer during their life span. The possibility to perform global gene expression profiling of tumor cells would likely provide important information of the genes and pathways that are involved in EAC susceptibility and carcinogenesis. Keywords: Endometrial tumors developed in crosses with the BDII inbred rat strain (from backcrosses, NUT, and intercrosses, RUT) and Sprague Dawley curley-3 and Brown Norway Common reference design - Universal rat reference (Stratagene) hybridized to all arrays. Biological replicates and technical replicates (3) of each clone printed at random positions on the array.
2010-05-19 | E-GEOD-13003 | biostudies-arrayexpress
Project description:Study question: Does a comprehensive study involving two different population cohorts and small RNA sequencing from endometrium and blood reveal new endometrial receptivity-related microRNAs (miRNAs) in healthy conditions and in women with recurrent implantation failure (RIF)? Summary answer: Several annotated miRNAs, not previously associated with endometrial receptivity, as well as one novel miRNA were found as differentially expressed between early secretory vs. mid-secretory phase samples in addition to miRNAs dysregulated in RIF patients. What is known already: The involvement of miRNAs in mid-secretory endometrial functions has been shown and aberrant expression of miRNAs in RIF has been identified in a few previous studies, but not from whole blood samples. However, as the analysis settings and platforms have been different and a small number of samples has been analysed, there is no consensus about the miRNAs involved in endometrial receptivity and dysfunction. Participants/materials, setting, methods: A total of 116 endometrial and 114 blood samples were subjected to Illumina small RNA sequencing. Identification of annotated and novel miRNAs from sequencing reads was performed by miRDeep2 algorithm. miRNAs that had significantly altered levels between the study groups in both EST and ESP datasets were considered as differentially expressed. Ingenuity Pathway Analysis was applied for identifying miRNA target genes and respective canonical pathways from the matched mRNA analysis from the same samples. Custom TaqMan Small RNA assay was used for the validation of novel miRNA (chr2_4401) levels from paired early secretory and mid-secretory endometrial samples. Main results and the role of chance: Among fertile women, 91 differentially expressed miRNAs were identified in mid-secretory vs. early secretory endometrium, while no differentially expressed miRNAs were found in the corresponding blood samples. The comparison of mid-secretory phase samples between fertile women and RIF patients revealed 21 differentially expressed miRNAs from endometrium and one from blood samples. miRNA target gene prediction analysis using our mRNA sequencing data from the matched samples detected several canonical pathways to be involved in mid-secretory endometrial functions, including JAK/STAT signalling, leptin signalling and growth hormone signalling. Moreover, JAK/STAT signalling pathway was also revealed in miRNA target analysis of mid-secretory endometrium from RIF patients when compared to fertile women. Further, our study results highlight the involvement of miR-30 and miR-200 families in endometrial receptivity, and miR-424-5p in the development of endometrial dysfunction. We identified several novel miRNAs, of which miRNA chr2_4401, being 37-fold up-regulated in mid-secretory phase, has a potential role in the mid-secretory endometrial functions. From blood samples we identified miR-30a-5p as a possible marker of infertility related to RIF.
2019-07-18 | GSE108966 | GEO
Project description:Transcriptional profiling of rat EAC - comparison of non-/pre-malignant endometrium with endometrial tumors Endometrial cancer develops from the endometrium of the uterus and is the most common pelvic malignancy diagnosed in women in the western countries. Similar to all cancer diseases, endometrial cancer is a genetic disorder that results from complex patterns of genetic and epigenetic alterations involved in the malignant transformation. The genetic heterogeneity inherent in the human population, differences in the environment and life styles poses enormous difficulties when analyzing the complex patterns of genetic alterations contributing to cancer etiology. Inbred animal models constitute unique experimental genetic tools as the genetic heterogeneity and the influence of environmental factors can be readily reduced. The BDII/Han rat model is unique for spontaneous hormonal carcinogenesis since more than 90% of the female virgins spontaneously develop endometrial cancer during their life span. The possibility to perform global gene expression profiling of tumor cells would likely provide important information of the genes and pathways that are involved in EAC susceptibility and carcinogenesis. Keywords: Endometrial tumors developed in crosses with the BDII inbred rat strain (from backcrosses, NUT, and intercrosses, RUT) and Sprague Dawley curley-3 and Brown Norway
2008-10-02 | GSE13003 | GEO
Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.
2016-01-15 | E-MTAB-3655 | biostudies-arrayexpress
Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.
2015-10-28 | E-MTAB-3713 | biostudies-arrayexpress
Project description:<p>We performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium, corresponding to the luteal phase of the ovarian cycle. Biopsies were collected from 58 women with two or more early pregnancy losses and 53 of these samples passed all quality control. RNA was extracted from endometrial biopsies and DNA was extracted for sequencing from blood.</p> <p>Gene expression data can be found at NCBI GEO Series GSE77688.</p>
| phs001146 | dbGaP