Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions

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

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Targeting of TAMs: can we be more clever than cancer cells?

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(12), P. 1376 - 1409

Published: Nov. 8, 2024

АBSTRACT: With increasing incidence and geography, cancer is one of the leading causes death, reduced quality life disability worldwide. Principal progress in development new anticancer therapies, improving efficiency immunotherapeutic tools, personification conventional therapies needs to consider cancer-specific patient-specific programming innate immunity. Intratumoral TAMs their precursors, resident macrophages monocytes, are principal regulators tumor progression therapy resistance. Our review summarizes accumulated evidence for subpopulations number biomarkers, indicating predictive value clinical parameters carcinogenesis resistance, with a focus on solid cancers non-infectious etiology. We present state-of-the-art knowledge about tumor-supporting functions at all stages highlight recently identified by single-cell spatial analytical methods, that discriminate between tumor-promoting tumor-inhibiting TAMs, where both subtypes express combination prototype M1 M2 genes. focuses novel mechanisms involved crosstalk among epigenetic, signaling, transcriptional metabolic pathways TAMs. Particular attention has been given link cell metabolism epigenetic histone lactylation, which can be responsible unlimited protumoral Finally, we explain how interfere currently used therapeutics summarize most advanced data from trials, divide into four categories: inhibition TAM survival differentiation, monocyte/TAM recruitment tumors, functional reprogramming genetic enhancement macrophages.

Language: Английский

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Update on the pathogenesis of endometriosis-related infertility based on contemporary evidence

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Endometriosis, the most prevalent cause of infertility, is associated with anatomical distortion leading to adhesions and fibrosis, as well endocrine abnormalities immune disorders. This review discusses mechanisms underlying endometriosis-related infertility. Firstly, alterations in hypothalamic-pituitary-ovarian axis lead secretion gonadotropins steroid hormones, adverse effects on ovulation implantation, fertility decline. Secondly, dysregulation hypothalamic-pituitary-adrenal induces elevated serum cortisol prolactin levels patients endometriosis, accounting for its regulation stress, depression, anxiety. Abnormal interactions between endometrial cells system change local microenvironment, resulting epithelial-mesenchymal transition inflammation. Activated epithelial cells, stromal immunocytes produce various chemokines, cytokines, or autoantibodies, creating an unfavorable environment embryo implantation. These findings suggest that spectrum play a crucial role Thirdly, oxidative stress has ovarian reserve subsequent embryonic development, predicting another promising strategy An unbalanced redox state, including impaired mitochondrial function, dysregulated lipid metabolism, iron-induced generates pro-oxidative which negatively impacts oocyte quality sperm viability. Thus, updated understanding involved this disease will help develop effective strategies manage

Language: Английский

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TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity

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

Published: Feb. 19, 2025

Language: Английский

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Oleanolic acid inhibits M2 macrophage polarization and potentiates anti-PD-1 therapy in hepatocellular carcinoma by targeting miR-130b-3p-PTEN-PI3K-AKT signaling and glycolysis

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156750 - 156750

Published: April 1, 2025

Language: Английский

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Single-cell and spatial transcriptomics reveal the pathogenesis of chronic granulomatous disease in a natural model

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115612 - 115612

Published: April 22, 2025

Language: Английский

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RNA sequencing reveals novel molecular mechanisms of endometriosis lesion development in a mouse model

Disease Models & Mechanisms, Journal Year: 2024, Volume and Issue: 17(10)

Published: Oct. 1, 2024

ABSTRACT Understanding of molecular mechanisms contributing to the pathophysiology endometriosis, and upstream drivers lesion formation, remains limited. Using a C57Bl/6 mouse model in which decidualized endometrial tissue is injected subcutaneously abdomen recipient mice, we generated comprehensive profile gene expression (n=4), endometriosis-like lesions at Day 7 (n=4) 14 formation. High-throughput mRNA sequencing allowed identification genes pathways involved initiation progression lesions. We observed distinct patterns with substantial differences between endometrium that remained stable across two timepoints, showed similarity transcriptional changes implicated human endometriosis Pathway enrichment analysis revealed several immune inflammatory response-associated canonical pathways, multiple potential regulators, involvement not previously pathogenesis, including IRF2BP2 ZBTB10, suggesting novel roles disease progression. Collectively, provided data will be useful resource inform research on development this model.

Language: Английский

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Editorial: Participant characteristics and biological markers for endometriosis diagnosis or prediction of treatment response

Frontiers in Reproductive Health, Journal Year: 2024, Volume and Issue: 6

Published: Dec. 19, 2024

and is associated with a range of symptoms, most commonly debilitating pelvic pain infertility [1].Standard practice for definitive endometriosis diagnosis has been through surgical visualization lesions. However, increasingly imaging being used to inform symptom management strategies certain subtypes, particularly when fertility treatment planned [1]. The invasive nature leads, in part, the average 7-year delay between onset [2]. Once person diagnosed endometriosis, conventional treatments include use hormonal medications suppress ovulation removal endometriotic lesions [1].Adding complexity diagnostic delays potential need additional surgeries, extensive heterogeneity presentation lesion characteristics [1].Endometriosis vary color, size, location, histopathologic metabolic characteristics, which may have important implications options. For example, recent review highlighted impact fibrosis within lesions, represent future therapeutic target [3]. Lesions more had higher numbers nerve cells, be linked increased symptoms Other studies suggested macrophages altered phenotypes found are basis recently launched clinical trial [TCS/23/19, MacEndo] [4]. further work needed expand on trials based targeting full evaluation their both symptoms. Additionally, there does not exist valid tool sufficient sensitivity specificity replace or triage laparoscopic surgery. Further, no biological markers algorithms determining patients will experience recurrent not.The aim this research topic was our understanding how that biomarkers and/or response.Incorporating informative disease into biomarker analyses critical obtaining results [5]. Two papers investigated among participants analyses. Although peritoneal fluid often identify terms color volume relation patient fully [6,7]. Yousif et al (2023) participant differ by 545 who enrolled Women's Health Study: from Adolescence Adulthood cohort study [8]. authors varied menstrual cycle phase, medication use, presence acyclic pain. appeared hormone pain.These suggest accounting phase utilizing discovery.Additionally, last 5 years increasing interest microRNAs (miRNAs), small non-coding RNAs involved epigenetic gene regulation, as [9], some potentially promising claimed saliva an accessible biofluid [10]. In special issue, Brady (2024) miRNAs blood samples during adolescence young adulthood measurements discovery (10 cases 10 controls) internal replication (54 108 group. During 49 were differentially expressed controls. study, miRNA score miR-545-3p, let-7b-3p, miR-548i, miR-769-5p, miR-30c-1-3p area under curve (AUC) 0.77 (95% confidence intervals: 0.67-0.87). While sufficiently sensitive specific enough tool, noted expression without differed use. These it account miRNAs, vast majority prior diagnosis.An component furthering investigating new describe differences subtypes support development personalized approaches therapy. To address challenge, Zoet developed standardized protocol assess bundle density 236 tissue 121 patients. novel protocol, calculated number bundles immunopositive PGP9.5 divided surface area. observed excellent intra-and inter-observer reliability importantly subtype. Higher deep superficial compared endometriomas. findings useful local neurogenesis advance differs impacts pathogenesis response disease.Finally, up 94% report complementary alternative methods coping endometriosis-associated [11], includes growing dietary modification [12]. known effectiveness these age group past focused largely adults confirmed diagnosis. gap knowledge, Mongiovi explored adolescents (age <18; n=137), 18-24; n=143), ≥25; n=77). They likely sleeping (57%) listening music (21%) helped (44% 7%, respectively) (43% 9%, respectively). Conversely, (11%) (15%) yoga improved (4%). exercise decrease age, 60% adolescents, 47% adults, 35% reporting made worse. highlight developing plans incorporate while taking accessibility acceptability approaches.The included acceptability. offer resource considering design research. Reflecting greater appreciation cancer revolutionized knowledge options cancers such breast [13], we believe increase data related vastly pathophysiology well aiding diagnostics

Language: Английский

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Geneticsbiologiesingle cell and expression analysis for erectile dysfunction and cervical cancer targets

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 21, 2024

Sexual dysfunction and cervical cancer are genetically molecularly two complex health problems. Here, we integrate genetic inference single-cell expression analysis to identify potential targets for sexual cancer, assess causality of these utilizing Mendelian randomization approaches. We performed a genome-wide association study (GWAS) variants associated with cancer. Next, examined the cellular landscape variation regions based on scRNAseq data. The identified several that correlated respectively, differentially expressed in reproductive cells. Two-Gene Combination Panel Increased WISP1 gene was detected tissues. Twas most highly T cells, least well- when cells were proliferating. integrates genetics nominate establishes causal support from approach.

Language: Английский

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