Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level DOI Creative Commons
Meruert Sarsenova, Ankita Lawarde, Amruta D. S. Pathare

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Aug. 21, 2024

Current therapeutics of endometriosis focus on hormonal disruption endometriotic lesions (ectopic endometrium, EcE). Recent findings show higher glycolysis utilization in EcE, suggesting non-hormonal strategy for disease treatment that addresses cellular metabolism. Identifying metabolically altered cell types EcE is important targeted metabolic drug therapy without affecting eutopic endometrium (EuE). Here, using single-cell RNA-sequencing, we examine twelve pathways paired samples EuE and from women with confirmed endometriosis. We detect nine major both EcE. Metabolic are most differentially regulated perivascular, stromal, endothelial cells, the highest changes AMPK signaling, HIF-1 glutathione metabolism, oxidative phosphorylation, glycolysis. identify transcriptomic co-activation glycolytic metabolism perivascular stromal cells indicating a critical role reprogramming maintaining lesion growth. Perivascular involved endometrial stroma repair angiogenesis, may be potential targets

Language: Английский

An integrated single-cell reference atlas of the human endometrium DOI Creative Commons

Magda Marečková,

Luz García‐Alonso,

Marie Moullet

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1925 - 1937

Published: Aug. 28, 2024

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors lacked consensus in defining cell types. We introduce Human Endometrial Cell Atlas (HECA), a high-resolution reference atlas (313,527 cells) combining published new transcriptomics datasets 63 women with without endometriosis. HECA assigns identifies previously unreported types, mapped situ using spatial validated independent single-nuclei dataset (312,246 nuclei, donors). In functionalis, we identify intricate stromal-epithelial coordination via transforming growth factor beta (TGFβ) signaling. basalis, define signaling between fibroblasts an epithelial population expressing progenitor markers. Integration large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells macrophages as most likely dysregulated is valuable resource for studying physiology disorders, guiding microphysiological vitro systems development.

Language: Английский

Citations

32
Endometriosis and autoimmunity DOI

Luz P. Blanco,

Noemi Salmeri, Sarah M. Temkin

et al.

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 103752 - 103752

Published: Jan. 1, 2025

Language: Английский

Citations

4
Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions DOI Creative Commons
Song Liu, Xiaoyan Li,

Zhiyue Gu

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: 5(1), P. 100737 - 100737

Published: Jan. 1, 2025

Highlights•Single-cell and spatial data reveal hierarchical microenvironment in endometriomas•Ectopic endometrial stromal cells retain menstrual cycle gene expression patterns•Distinct ovarian (OSCs) links to fibrosis inflammation lesions•WNT5A signaling mediates interactions between ectopic OSCsSummaryEndometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting attachment the local sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell transcriptomic profiling lesions eutopic endometrium endometriosis. We found that (EnS) retained cyclical patterns their counterparts while exhibiting unique contributes pathogenesis identified two distinct localized at different zones lesion, showing differential profiles associated inflammation, respectively. also WNT5A upregulation aberrant activation non-canonical WNT may contribute establishment, offering novel targets for intervention. These will enhance our understanding mechanisms underlying endometriosis paves way developing non-hormonal treatments.Graphical abstract

Language: Английский

Citations

3
The Estrogen–Immune Interface in Endometriosis DOI Creative Commons

Emily Greygoose,

Pat Metharom, Hakan Kula

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(1), P. 58 - 58

Published: Jan. 6, 2025

Endometriosis is a gynecologic condition characterized by the growth of endometrium-like stroma and glandular elements outside uterine cavity. The involvement hormonal dysregulation, specifically estrogen, well established in initiation, progression, maintenance condition. Evidence also highlights association between endometriosis altered immune states. human endometrium highly dynamic tissue that undergoes frequent remodeling response to regulation during menstrual cycle. Similarly, shares this propensity, compounded unclear pathogenic mechanisms, presenting unique challenges defining its etiology pathology. Here, we provide lens understand interplay estrogen innate adaptive systems throughout cycle pathogenesis endometriosis. Estrogen closely linked many inflammatory immunomodulatory states, affecting both tissue-resident circulatory cells. This review summarizes estrogenic interactions with specific myeloid lymphoid cells, highlighting their implications progression

Language: Английский

Citations

2
FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy DOI Creative Commons
Na Zhang, Yang Meng,

Song Mao

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 2, 2025

Protein O-GlcNAcylation is a post-translational modification coupled to cellular metabolic plasticity. Aberrant has been observed in many cancers including endometrial cancer (EC), common malignancy women. However, clinical characterization of dysregulated homeostasis EC and interrogating its molecular mechanism remain incomplete. Here we report that level positively correlated with histologic grade Chinese cohort containing 219 tumors, validated The Cancer Genome Atlas dataset. Increasing patient-derived epithelial organoids promotes proliferation stem-like cell properties, whereas decreasing limits the growth organoids. CRISPR screen biochemical reveal tumor suppressor F-box only protein 31 (FBXO31) regulates by ubiquitinating O-GlcNAc transferase OGT. Downregulation impedes formation mouse models. Collectively, our study highlights as useful stratification marker therapeutic vulnerability for advanced, poorly differentiated cases. linked (EC). authors grade, FBXO31

Language: Английский

Citations

2
Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations DOI Creative Commons
Linda C. Giudice, Tomiko Oskotsky, Simileoluwa Falako

et al.

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(9)

Published: Aug. 29, 2023

Endometriosis is a common estrogen-dependent disorder wherein uterine lining tissue (endometrium) found mainly in the pelvis where it causes inflammation, chronic pelvic pain, pain with intercourse and menses, infertility. Recent evidence also supports systemic inflammatory component that underlies associated co-morbidities, e.g., migraines cardiovascular autoimmune diseases. Genetics environment contribute significantly to disease risk, explosion of omics technologies, underlying mechanisms symptoms are increasingly being elucidated, although novel effective therapeutics for infertility have lagged behind these advances. Moreover, there stark disparities diagnosis, access care, treatment among persons color transgender/nonbinary identity, socioeconomically disadvantaged populations, adolescents, disturbing low awareness health care providers, policymakers, lay public about endometriosis, which, if left undiagnosed under-treated can lead significant fibrosis, infertility, depression, markedly diminished quality life. This review summarizes endometriosis epidemiology, compelling its pathogenesis, pathophysiology age precision medicine, recent biomarker discovery, therapeutic approaches, issues around reproductive justice marginalized populations this spanning past 100 years. As we enter next revolution biomedical research, rich molecular clinical datasets, single-cell omics, population-level data, well positioned benefit from data-driven research leveraging computational artificial intelligence approaches integrating data predicting response medical surgical therapies, prognosis recurrence.

Language: Английский

Citations

33
Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement DOI Creative Commons

Nicolas Monnin,

Anne Julie Fattet,

Isabelle Koscinski

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 978 - 978

Published: March 22, 2023

Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to pain and impaired fertility. Characterized their dependence on estradiol (via estrogen receptor β (ESRβ)) resistance progesterone, endometriotic produce own source of through active aromatase. Steroidogenic factor-1 (SF1) key transcription factor that promotes aromatase synthesis. The expression SF1 ESRβ enhanced the demethylation promoter in progenitor cells female reproductive system. High local concentrations are involved inflammatory environment favoring implantation development implants. Similar conditions can promote, directly indirectly, appearance genital cancer. Recently, certain components microbiota have been identified as potentially promoting high level blood. Many environmental factors also suspected increasing concentration, especially prenatal exposure estrogen-like endocrine disruptors such DES bisphenol A. Phthalates endometriosis but throughmeans other than binding receptors. impact dioxin or tobacco seems be more controversial.

Language: Английский

Citations

30
Systems level identification of a matrisome-associated macrophage polarisation state in multi-organ fibrosis DOI Creative Commons
John F. Ouyang, Kunal Mishra, Yi Xie

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Sept. 14, 2023

Tissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms fibrosis. The recently unravelled multi-organ heterogeneity healthy fibrotic human disease suggests that expressing osteopontin (SPP1) associate with lung liver However, the conservation this SPP1+ macrophage population across different tissues its specificity diseases etiologies remain unclear. Integrating 15 single-cell RNA-sequencing datasets profile 235,930 tissue from heart, lung, liver, kidney, skin, endometrium, we extended association these tissues. We also identified subpopulation matrisome-associated genes (e.g., matrix metalloproteinases their inhibitors), functionally enriched for ECM remodelling cell metabolism, representative (MAM) polarisation state within macrophages. Importantly, MAM follows differentiation trajectory is associated core set regulon activity. without (SPP1+MAM-) show positive ageing mice humans. These results suggest advanced conserved resulting prolonged cues each microenvironment.

Language: Английский

Citations

26
Single-cell analysis reveals insights into epithelial abnormalities in ovarian endometriosis DOI Creative Commons
Jia Yan, Ling Zhou, Mengya Liu

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113716 - 113716

Published: Feb. 26, 2024

Ovarian endometriosis is characterized by the growth of endometrial tissue within ovary, causing infertility and chronic pain. However, its pathophysiology remains unclear. Utilizing high-precision single-cell RNA sequencing, we profile normal, eutopic, ectopic endometrium from 34 individuals across proliferative secretory phases. We observe an increased proportion ciliated cells in both eutopic endometrium, a diminished expression estrogen sulfotransferase, which likely confers apoptosis resistance. After translocating to lesions, epithelium upregulates nicotinamide N-methyltransferase that inhibits promoting deacetylation subsequent nuclear exclusion transcription factor forkhead box protein O1, thereby leading downregulation apoptotic gene BIM. Moreover, epithelial lesions elevate HLA class II complex expression, stimulates CD4

Language: Английский

Citations

12
Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis DOI Creative Commons
Pooya Farhangnia, Morvarid Noormohammadi, Ali‐Akbar Delbandi

et al.

Reproductive Health, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 2, 2024

Abstract Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels maintaining bone health. However, it later discovered many organs express vitamin metabolizing enzymes have ligand D, which regulates the expression of an extensive assortment genes. As result, indispensable proper function organs, its deficiency believed to be critical factor in symptoms disorders such as cardiovascular diseases, autoimmune cancers. The significance reproductive tissues recognized later, studies revealed crucial role male female fertility, well during pregnancy. has been identified risk infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, endometriosis. data investigating association between disorders, including endometriosis, encountered inconsistencies. Therefore, present study aims review existing research on effect function, diseases specifically focuses

Language: Английский

Citations

12