Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Science, Journal Year: 2022, Volume and Issue: 376(6594)

Published: May 12, 2022

Understanding gene function and regulation in homeostasis disease requires knowledge of the cellular tissue contexts which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen types from 16 donors 25 samples, generating a cross-tissue atlas 209,126 nuclei profiles, integrated across tissues, donors, laboratory with conditional variational autoencoder. Using resulting atlas, highlight shared tissue-specific features tissue-resident cell populations; identify that might contribute neuromuscular, metabolic, immune components monogenic diseases biological processes involved their pathology; determine modules underlie mechanisms for complex traits analyzed by genome-wide association studies.

Language: Английский

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A spatially resolved single-cell genomic atlas of the adult human breast

Nature, Journal Year: 2023, Volume and Issue: 620(7972), P. 181 - 191

Published: June 28, 2023

Language: Английский

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Cellular interactions in tumor microenvironment during breast cancer progression: new frontiers and implications for novel therapeutics

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 12, 2024

The breast cancer tumor microenvironment (TME) is dynamic, with various immune and non-immune cells interacting to regulate progression anti-tumor immunity. It now evident that the within TME significantly contribute resistance conventional newly developed therapies. Both in play critical roles onset, uncontrolled proliferation, metastasis, evasion, Consequently, molecular cellular components of have emerged as promising therapeutic targets for developing novel treatments. primarily comprises cells, stromal vasculature, infiltrating cells. Currently, numerous clinical trials targeting specific are underway. However, complexity its impact on evasion immunity necessitate further research develop improved multifaceted nature arises from their phenotypic functional plasticity, which endows them both pro during progression. In this review, we discuss current understanding recent advances anti-tumoral functions implications safe effective therapies control progress.

Language: Английский

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Novel molecular regulators of breast cancer stem cell plasticity and heterogeneity

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 82, P. 11 - 25

Published: March 18, 2021

Tumors consist of heterogeneous cell populations, and tumor heterogeneity plays key roles in regulating tumorigenesis, metastasis, recurrence resistance to anti-tumor therapies. More more studies suggest that cancer stem cells (CSCs) promote drug as well are the major source for cells. CD24-CD44+ ALDH+ most common markers breast (BCSCs). Previous showed different BCSC label indicating BCSCs. Therefore, defining regulation mechanisms BCSCs is essential precisely targeting treating cancer. In this review, we summarized novel regulators existed their niches which has been discovered recent years, discussed latest corresponding treatments, will extend our understanding on plasticity, provide better prognosis prediction efficient therapeutic strategies

Language: Английский

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The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Feb. 14, 2022

Abstract Obesity is nowadays considered a pandemic which prevalence’s has been steadily increasingly in western countries. It dynamic, complex, and multifactorial disease propitiates the development of several metabolic cardiovascular diseases, as well cancer. Excessive adipose tissue causally related to cancer progression preventable risk factor for overall cancer-specific survival, associated with poor prognosis patients. The onset obesity features state chronic low-grade inflammation secretion diversity adipocyte-derived molecules (adipokines, cytokines, hormones), responsible altering metabolic, inflammatory, immune landscape. crosstalk between adipocytes tumor cells fuels microenvironment pro-inflammatory factors, promoting injury, mutagenesis, invasion, metastasis. Although classically established treatment toxicity, recent evidence suggests mild better outcomes, obese patients showing responses when compared lean This phenomenon termed paradox reported different types stages mechanisms underlying this paradoxical relationship are still not fully described but point systemic alterations fitness modulation by obesity-associated molecules. impacts response treatments, such chemotherapy immunotherapy, having positive association checkpoint therapy. In review, we discuss obesity’s cancer, also highlighting potential physiological biological association, hoping clarify existence impact treatment.

Language: Английский

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Weight Gain in Midlife Women

Current Obesity Reports, Journal Year: 2024, Volume and Issue: 13(2), P. 352 - 363

Published: Feb. 28, 2024

Language: Английский

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Hypoxia-mediated drug resistance in breast cancers

Cancer Letters, Journal Year: 2020, Volume and Issue: 502, P. 189 - 199

Published: Dec. 3, 2020

Language: Английский

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The Effects of Ionising and Non-Ionising Electromagnetic Radiation on Extracellular Matrix Proteins

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3041 - 3041

Published: Nov. 5, 2021

Exposure to sub-lethal doses of ionising and non-ionising electromagnetic radiation can impact human health well-being as a consequence of, for example, the side effects radiotherapy (therapeutic X-ray exposure) accelerated skin ageing (chronic exposure ultraviolet radiation: UVR). Whilst attention has focused primarily on interaction with cells cellular components, radiation-induced damage long-lived extracellular matrix (ECM) proteins potential profoundly affect tissue structure, composition function. This review focuses current understanding biological ECM breast stroma dermis, respectively. Although there is some experimental evidence proteins, compared well-characterised cell biology, structural, functional, ultimately clinical consequences irradiation remain poorly defined.

Language: Английский

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The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 16, 2022

Abstract The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide increased gradually. Most them are listed on the table high-risk factors for malignancy, metabolic disorders systematically or locally contribute to cancer progression poor prognosis patients. Importantly, adipose tissue is fundamental occurrence development these disorders. White stores excessive energy, while thermogenic fat including brown beige dissipates energy generate heat. In addition thermogenesis, adipocytes also function as dynamic secretory cells a sink nutrients, glucose, fatty acids, amino acids. Accordingly, strategies that activate expand offer therapeutic promise combat overweight, diabetes, other through increasing expenditure enhancing glucose tolerance. With better understanding its origins biological functions advances in imaging techniques detecting roles tumors have been revealed On one hand, enhanced browning subcutaneous results weight loss cancer-associated cachexia. activated tumor microenvironment accelerate by offering fuel sources likely develop resistance chemotherapy. Here, we enumerate current knowledge about significant made origin physiological fat. addition, discuss multiple different tumors. Ultimately, summarize technologies identifying pharmacologic agents via modulating thermogenesis preclinical experiments clinical trials.

Language: Английский

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BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4982 - 4982

Published: March 5, 2023

Two related tumor suppressor genes, BRCA1 and BRCA2, attract a lot of attention from both fundamental clinical points view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset breast ovarian cancers. However, molecular mechanisms that drive extensive mutagenesis not known. In this review, we hypothesize one potential behind phenomenon can be mediated by Alu mobile genomic elements. Linking BRCA2 general genome stability DNA repair is critical ensure rationalized choice anti-cancer therapy. Accordingly, review literature available on damage where proteins involved, how inactivating (BRCAness) exploited We also discuss hypothesis explaining why epithelial tissues preferentially susceptible BRCA genes. Finally, prospective novel therapeutic approaches for treating BRCAness

Language: Английский

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