CITEgeist: Cellular Indexing of Transcriptomes and Epitopes for Guided Exploration of Intrinsic Spatial Trends

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

ABSTRACT Spatial transcriptomics provides insights into tissue architecture by linking gene expression with spatial localization. Current deconvolution methods rely heavily on single-cell RNA sequencing (scRNA-seq) references, which are costly and often unavailable, mainly if the under evaluation is limited, such as in a core biopsy specimen. We present novel tool, CITEgeist, that deconvolutes data using antibody capture from same slide reference, directly leveraging cell surface protein measurements section. This approach circumvents limitations of scRNA-seq offering cost-effective biologically grounded alternative. Our method employs mathematical optimization to estimate type proportions profiles, incorporating sparsity constraints for robustness interpretability. Benchmarks against state-of-the-art show improved accuracy resolution, particularly dense tumor microenvironments, while maintaining computational efficiency. antibody-based tool advances providing scalable, accurate, reference-independent solution complex tissues. validate this combined simulated clinical samples applying CITEgeist translational pre-treatment post-treatment ER+ breast tumors an ongoing trial, emphasizing applicability CITEgeist.

Language: Английский

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Decoding the crossroads of aging and cancer through single‐cell analysis: Implications for precision oncology

International Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract Single‐cell analysis is a transformative approach to understanding cellular heterogeneity in aging and cancer, interconnected processes driven by mechanisms like senescence immune modulation. This review explores how influences cancer initiation, progression, treatment resistance within the tumor microenvironment (TME). By examining recent studies using single‐cell technologies, we reveal nuanced roles of tumorigenesis, interactions, therapeutic outcomes. Aging closely tied with senescent cells demonstrating heightened proliferative, invasive, metastatic capabilities. Emerging senolytic therapies targeting aging‐related pathways hold promise for enhancing efficacy. Advanced tools such as spatial transcriptomics, molecular probes, artificial intelligence further refine our TME. integrating these future research can clarify intricate interactions between advancing precision oncology improving outcomes patients.

Language: Английский

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Endometrial Stromal Senescence Mediates the Progression of Intrauterine Adhesions

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4183 - 4183

Published: April 28, 2025

Cellular senescence has emerged as a key mediator in organ-specific fibrosis. Here, we have established the role of endometrial stromal progression fibrosis, termed intrauterine adhesions (IUA). IUA significant negative effects on women’s reproductive health and are associated with infertility. We generated original gene signatures to identify single-cell bulk RNA-sequencing data. By applying signatures, revealed an increased level during proliferative phase endometrium patients IUA. Further comparative analysis cell–cell communications demonstrated that senescent cells create immunosuppressive profibrotic microenvironment through elevated expression LGALS9. Endometrial persists window implantation correlates impaired embryo receptivity endometrium. Therefore, can be regarded primary cause unresponsive decreased thickness patients. A LGALS9 immunotherapy protocol, specifically designed neutralize activity cells, may offer promising opportunity restore effective immune clearance these within stroma. Consequently, LGALS9-based strategy could emerge novel therapeutic avenue treatment

Language: Английский

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Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer

Nature Aging, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation unknown. In this study, we investigated aging rewires transcriptomic epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource biology. Aged epithelial cells exhibit epigenetic transcriptional changes in metabolic, pro-inflammatory cancer-associated genes. stromal downregulate fibroblast marker genes upregulate markers senescence fibroblasts. Among immune cells, distinct T cell subsets (Gzmk

Language: Английский

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Midkine links aging with breast cancer—A new predictor of cancer risk

Cancer Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Systemic and local chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract Estrogen receptor positive (ER+) breast cancer is the most common subtype of and an age-related disease. The peak incidence diagnosis occurs around age 70, even though these post-menopausal patients have low circulating levels estradiol (E2). Despite hormone sensitivity tumors, we a limited understanding interplay between systemic local hormones, chronic inflammation, immune changes that contribute to growth development tumors. Here, show aged F344 rats treated with dimethylbenz(a)anthracene / medroxyprogestrone acetate (DMBA/MPA) carcinogen develop more tumors at faster rates than their younger counterparts, suggesting environment promotes tumor initiation impacts growth. Single-nuclei RNA-seq (snRNA-seq) showed broad dysfunction was associated inflammation. Across cohort specimens from ER+ age-matched donors normal tissue, observe estrone (E1)-predominant estrogen disposition in circulation, older increase HSD17B7 expression convert E1 E2 microenvironment (TME) similar pre-menopausal patients. Concurrently, trackable increases several chemokines, defined notably by CCL2, promote chronically inflamed but dysfunctional TME. This unique milieu TME, characterized high chemokine-enriched both accumulation tumor-associated macrophages (TAMs), which serve as signaling hubs, well polarization TAMs towards CD206+/PD-L1+, immunosuppressive phenotype. Pharmacologic targeting (either inhibition or fulvestrant) chemokine inflammation decrease prevent macrophage polarization. Overall, findings suggest hormonal are critical contributors nature offer potential therapeutic insight treat Translational Summary We uncover underpinnings establishing how host contributes microenvironment, dysregulation, avenues conversion work restore anti-tumor immunity. Graphical

Language: Английский

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Midkine crisis fuels age-related tumorigenesis

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(12), P. 828 - 828

Published: Oct. 31, 2024

Language: Английский

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