Dataset Information

What do the transcriptome and proteome of menstrual blood derived mesenchymal stem cells tell us about endometriosis?

ABSTRACT: Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data is for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. It is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC- MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, and response to hypoxia via HIF1A targets (↑in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Vitor Faca

LAB HEAD: Juliana Meola

PROVIDER: PXD037033 | Pride | 2023-03-11

REPOSITORIES: Pride

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What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

Penariol Letícia B C LBC Thomé Carolina H CH Tozetti Patrícia A PA Paier Carlos R K CRK Buono Fabiana O FO Peronni Kamila C KC Orellana Maristela D MD Covas Dimas T DT Moraes Maria E A MEA Silva Wilson A WA Rosa-E-Silva Júlio C JC Ferriani Rui A RA Faça Vitor M VM Poli-Neto Omero B OB Tiezzi Daniel G DG Meola Juliana J

International journal of molecular sciences 20220929 19

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hosp ...[more]

PMID: 36232817

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Project description:Endometriosis, an estrogen-dependent, progesterone-resistant, inflammatory disorder affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Since the uterine lining (endometrium) in women with endometriosis has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n=148 archived endometrial samples from women with endometriosis or without endometriosis (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with endometriosis or no endometriosis involved two binary decisions each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no endometriosis from endometriosis, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified endometriosis with 90-100% accuracy, were cycle phase-specific or independent, and utilized relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism and growth factor signaling in endometrium of women with endometriosis. Similar findings were observed with other disorders versus controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic endometriosis with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate-genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of endometriosis and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue. We analyzed endometrial samples from n=148 women without or with endometriosis and/or other uterine/pelvic pathologies, using whole genome microarrays.

Project description:Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected at 9-11 days postovulation) in five time points: 1, 3, 6-7, 10-12, and 15-16 months after disease induction and compared with tissue from disease-free baboons. We used microarrays to identify differentially expressed genes between time points. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype. However, as the disease progressed, a progesterone-resistant phenotype became evident. Endometriosis was experimentally induced in Papio anubis female baboons (n = 4) by intraperitoneal inoculation with menstrual endometrium on two consecutive menstrual cycles. Baboons with spontaneous endometriosis (n = 2) were also included in this study with an unknown duration of disease. Control endometrium was similarly harvested from animals (n = 4) with no previous surgeries and with no visible disease. The progression of disease was monitored in each animal by consecutive laparoscopies and video recording at 1 (n = 2), 3 (n = 4), 6-7 (n = 4), 10-12, (n = 4), and 15-16 (n = 3) months after inoculation during a window of 9-11 days postovulation. Eutopic endometrial tissues were harvested and were snap frozen in liquid nitrogen for RNA extraction. Additionally, menstrual endometrium was harvested on Days 1-2 of menses using a Unimar Pipelle (Cooper Surgical Inc., Shelton, CT) immediately prior to laparoscopy. Blood samples were collected daily from days 7 through 16 postmenstruation of menstrual cycles.

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