Single-cell omics in inflammatory bowel disease: recent insights and future clinical applications DOI Creative Commons
Victòria Gudiño, Raquel Bartolomé-Casado, Azucena Salas

и другие.

Gut, Год журнала: 2025, Номер unknown, С. gutjnl - 334165

Опубликована: Фев. 4, 2025

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all cell types, including immune, epithelial stromal cells, have been described these diseases. The study IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse limiting insights. Single-cell omic technologies overcome intrinsic limitations analysis reveal complexity multicellular tissues at a cell-by-cell resolution. Within healthy inflamed tissues, single-cell omics, particularly RNA sequencing, contributed to uncovering novel types functions linked activity or development complications. Collectively, results help identify therapeutic targets difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae pouch. More recently, omics gradually adopted studies understand responses, mechanisms drug failure potentially develop predictors with clinical utility. Although early days, lay groundwork for implementation practice new diagnostics, monitoring prediction prognosis. With review, we aim provide comprehensive survey that applied UC CD, offer our perspective main findings contribute. Finally, discuss potential benefits integration into could offer.

Язык: Английский

IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies DOI Creative Commons
Matthias Friedrich, Mathilde Pohin, Matthew Jackson

и другие.

Nature Medicine, Год журнала: 2021, Номер 27(11), С. 1970 - 1981

Опубликована: Окт. 21, 2021

Abstract Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology situ localization across three cohorts patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular response that map to distinct histopathological cellular features (pathotypes). One these pathotypes is defined by neutrophil infiltration, activation fibroblasts vascular remodeling at sites deep ulceration. Activated ulcer bed display neutrophil-chemoattractant properties IL-1R, but not TNF, dependent. Pathotype-associated fibroblast signatures increased nonresponders several four independent 343). The identification distinct, localized, will aid precision targeting current therapeutics provides biological rationale for IL-1 signaling blockade ulcerating disease.

Язык: Английский

Процитировано

193
Efficient and precise single-cell reference atlas mapping with Symphony DOI Creative Commons
Joyce B. Kang, Aparna Nathan, Kathryn Weinand

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Окт. 7, 2021

Abstract Recent advances in single-cell technologies and integration algorithms make it possible to construct comprehensive reference atlases encompassing many donors, studies, disease states, sequencing platforms. Much like mapping reads a genome, is essential be able map query cells onto complex, multimillion-cell rapidly identify relevant cell states phenotypes. We present Symphony ( https://github.com/immunogenomics/symphony ), an algorithm for building large-scale, integrated convenient, portable format that enables efficient within seconds. localizes stable low-dimensional embedding, facilitating reproducible downstream transfer of reference-defined annotations the query. demonstrate power multiple real-world datasets, including (1) multi-donor, multi-species predict pancreatic types, (2) localizing along developmental trajectory fetal liver hematopoiesis, (3) inferring surface protein expression with multimodal CITE-seq atlas memory T cells.

Язык: Английский

Процитировано

164
Fibroblast pathology in inflammatory diseases DOI Open Access
Kevin Wei,

Hung Nguyen,

Michael B. Brenner

и другие.

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(20)

Опубликована: Окт. 14, 2021

Fibroblasts are important cells for the support of homeostatic tissue function. In inflammatory diseases such as rheumatoid arthritis and bowel disease, fibroblasts take on different roles (a) themselves (b) in recruiting leukocytes, driving angiogenesis, enabling chronic inflammation tissues. Recent advances single-cell profiling techniques have transformed ability to examine fibroblast states populations inflamed tissues, providing evidence previously underappreciated heterogeneity disease-associated populations. These studies challenge preconceived notion that homogeneous provide new insights into role pathology. addition, molecular mechanisms activation reveal powerful cell-intrinsic amplification loops synergize with primary stimuli result striking responses. this Review, we focus recent developments our understanding pathology across tissues diseases. We highlight approaches to, applications of, what they teach us about biology. Finally, address how these could lead development novel therapeutic targeting disease.

Язык: Английский

Процитировано

158
Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes DOI Creative Commons
Fan Zhang, A. Helena Jonsson, Aparna Nathan

и другие.

Nature, Год журнала: 2023, Номер 623(7987), С. 616 - 624

Опубликована: Ноя. 8, 2023

Abstract Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction 1 . There currently no cure for rheumatoid arthritis, the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity 1,2 Here, to deconstruct cell states pathways characterize this heterogeneity, we profiled full spectrum cells in inflamed synovium from patients with arthritis. We used multi-modal single-cell RNA-sequencing surface protein data coupled histology synovial tissue 79 donors build atlas includes more than 314,000 cells. stratified tissues into six groups, referred as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched states. These CTAPs demonstrate ranging samples T B those largely lacking lymphocytes. Disease-relevant states, cytokines, risk genes, serology metrics are associated particular CTAPs. dynamic can predict treatment response, highlighting clinical utility classifying phenotypes. This comprehensive molecular, tissue-based stratification reveal new insights pathology heterogeneity could inform novel targeted treatments.

Язык: Английский

Процитировано

142
The advent of immune stimulating CAFs in cancer DOI
Maria Tsoumakidou

Nature reviews. Cancer, Год журнала: 2023, Номер 23(4), С. 258 - 269

Опубликована: Фев. 17, 2023

Язык: Английский

Процитировано

76
Immunology of human fibrosis DOI
Mallar Bhattacharya, Prakash Ramachandran

Nature Immunology, Год журнала: 2023, Номер 24(9), С. 1423 - 1433

Опубликована: Июль 20, 2023

Язык: Английский

Процитировано

65
Vascular cells improve functionality of human cardiac organoids DOI Creative Commons
Holly K. Voges, Simon R. Foster, Liam Reynolds

и другие.

Cell Reports, Год журнала: 2023, Номер 42(5), С. 112322 - 112322

Опубликована: Апрель 26, 2023

Crosstalk between cardiac cells is critical for heart performance. Here we show that vascular within human organoids (hCOs) enhance their maturation, force of contraction, and utility in disease modeling. Herein optimize our protocol to generate populations addition epicardial, fibroblast, cardiomyocyte self-organize into in-vivo-like structures hCOs. We identify mechanisms communication endothelial cells, pericytes, fibroblasts, cardiomyocytes ultimately contribute organoid maturation. In particular, (1) endothelial-derived LAMA5 regulates expression mature sarcomeric proteins contractility, (2) paracrine platelet-derived growth factor receptor β (PDGFRβ) signaling from upregulates matrix deposition augment hCO contractile force. Finally, demonstrate determine the magnitude diastolic dysfunction caused by inflammatory factors a role endothelin driving dysfunction. Together this study highlights importance models.

Язык: Английский

Процитировано

63
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy DOI
Jonathan H. Chen, Linda T. Nieman, Maxwell Spurrell

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(4), С. 644 - 658

Опубликована: Март 19, 2024

Язык: Английский

Процитировано

51
Alveolar fibroblast lineage orchestrates lung inflammation and fibrosis DOI
Tatsuya Tsukui, Paul J. Wolters, Dean Sheppard

и другие.

Nature, Год журнала: 2024, Номер 631(8021), С. 627 - 634

Опубликована: Июль 10, 2024

Язык: Английский

Процитировано

45
The cycling and aging mouse female reproductive tract at single-cell resolution DOI Creative Commons
Ivana Winkler, Alexander Tolkachov, Fritjof Lammers

и другие.

Cell, Год журнала: 2024, Номер 187(4), С. 981 - 998.e25

Опубликована: Фев. 1, 2024

The female reproductive tract (FRT) undergoes extensive remodeling during cycling. This recurrent and how it shapes organ-specific aging remains poorly explored. Using single-cell spatial transcriptomics, we systematically characterized morphological gene expression changes occurring in ovary, oviduct, uterus, cervix, vagina at each phase of the mouse estrous cycle, decidualization, into aging. These analyses reveal that fibroblasts play central-and highly organ-specific-roles FRT by orchestrating extracellular matrix (ECM) reorganization inflammation. Our results suggest a model wherein over lifespan drives gradual, age-related development fibrosis chronic hypothesis was directly tested using chemical ablation cycling, which reduced fibrotic accumulation atlas provides detail estrus, pregnancy, shape organs reveals unexpected cost required for reproduction.

Язык: Английский

Процитировано

34