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单细胞 RNA 测序分析以提高人类 IBD 与模型之间的转化。

Single cell RNA-sequencing profiling to improve the translation between human IBD and models.

机构信息

Bioscience Immunology, Research and Early Development, Respiratory and Immunology, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.

Bioscience Immunology, Research and Early Development, Respiratory and Immunology, Biopharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.

出版信息

Front Immunol. 2023 Dec 19;14:1291990. doi: 10.3389/fimmu.2023.1291990. eCollection 2023.


DOI:10.3389/fimmu.2023.1291990
PMID:38179052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10766350/
Abstract

Inflammatory bowel disease (IBD) is an umbrella term for two conditions (Crohn's Disease and Ulcerative Colitis) that is characterized by chronic inflammation of the gastrointestinal tract. The use of pre-clinical animal models has been invaluable for the understanding of potential disease mechanisms. However, despite promising results of numerous therapeutics in mouse colitis models, many of these therapies did not show clinical benefits in patients with IBD. Single cell RNA-sequencing (scRNA-seq) has recently revolutionized our understanding of complex interactions between the immune system, stromal cells, and epithelial cells by mapping novel cell subpopulations and their remodeling during disease. This technology has not been widely applied to pre-clinical models of IBD. ScRNA-seq profiling of murine models may provide an opportunity to increase the translatability into the clinic, and to choose the most appropriate model to test hypotheses and novel therapeutics. In this review, we have summarized some of the key findings at the single cell transcriptomic level in IBD, how specific signatures have been functionally validated , and highlighted the similarities and differences between scRNA-seq findings in human IBD and experimental mouse models. In each section of this review, we highlight the importance of utilizing this technology to find the most suitable or translational models of IBD based on the cellular therapeutic target.

摘要

炎症性肠病(IBD)是两种疾病(克罗恩病和溃疡性结肠炎)的总称,其特征是胃肠道的慢性炎症。临床前动物模型的使用对于理解潜在的疾病机制非常有价值。然而,尽管在小鼠结肠炎模型中许多治疗方法取得了有希望的结果,但其中许多治疗方法在 IBD 患者中并未显示出临床益处。单细胞 RNA 测序(scRNA-seq)通过绘制新型细胞亚群及其在疾病过程中的重塑,最近彻底改变了我们对免疫系统、基质细胞和上皮细胞之间复杂相互作用的理解。这项技术尚未广泛应用于 IBD 的临床前模型。对小鼠模型进行 scRNA-seq 分析可能为提高其向临床转化的能力提供机会,并选择最合适的模型来检验假设和新型治疗方法。在这篇综述中,我们总结了 IBD 单细胞转录组水平的一些关键发现,如何对特定特征进行功能验证,并强调了人类 IBD 和实验性小鼠模型中 scRNA-seq 发现的相似性和差异。在这篇综述的每一部分,我们都强调了基于细胞治疗靶点利用这项技术寻找最合适或最具转化潜力的 IBD 模型的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c902/10766350/5a6da6148214/fimmu-14-1291990-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c902/10766350/7a60da97644e/fimmu-14-1291990-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c902/10766350/5a6da6148214/fimmu-14-1291990-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c902/10766350/7a60da97644e/fimmu-14-1291990-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c902/10766350/5a6da6148214/fimmu-14-1291990-g002.jpg

相似文献

[1]
Single cell RNA-sequencing profiling to improve the translation between human IBD and models.

Front Immunol. 2023

[2]
The landscape of miRNA-mRNA regulatory network and cellular sources in inflammatory bowel diseases: insights from text mining and single cell RNA sequencing analysis.

Front Immunol. 2024

[3]
High-resolution gene expression profiling using RNA sequencing in patients with inflammatory bowel disease and in mouse models of colitis.

J Crohns Colitis. 2015-3-20

[4]
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Gastroenterology. 2021-4

[5]
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Gastroenterology. 2020-8

[6]
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Inflamm Bowel Dis. 2021-11-15

[7]
Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn's Disease and Colorectal Cancer.

Int J Mol Sci. 2022-3-12

[8]
Single-cell meta-analysis of inflammatory bowel disease with scIBD.

Nat Comput Sci. 2023-6

[9]
Review of Saccharomyces boulardii as a treatment option in IBD.

Immunopharmacol Immunotoxicol. 2018-5-17

[10]
Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD.

BMC Immunol. 2019-11-12

引用本文的文献

[1]
Gut-heart axis: cardiac remodeling and heart failure in the context of inflammatory bowel disease and dysbiosis.

Am J Physiol Gastrointest Liver Physiol. 2025-7-1

[2]
Regulatory role of CD177+ neutrophils in BMP signaling pathway and its implications for inflammatory bowel disease, sepsis, and intestinal tumors.

Transl Oncol. 2025-5

[3]
Xanthohumol ameliorates dextran sodium sulfate-induced colitis in mice by inhibiting of NF-κB signaling pathways and modulating intestinal microbiota.

Eur J Nutr. 2024-11-22

本文引用的文献

[1]
Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling.

Cell. 2024-4-11

[2]
Single-cell meta-analysis of inflammatory bowel disease with scIBD.

Nat Comput Sci. 2023-6

[3]
Stricturing Crohn's Disease Single-Cell RNA Sequencing Reveals Fibroblast Heterogeneity and Intercellular Interactions.

Gastroenterology. 2023-11

[4]
Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.

Nat Commun. 2023-7-26

[5]
The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.

Cell Rep Med. 2023-5-16

[6]
Human intestinal B cells in inflammatory diseases.

Nat Rev Gastroenterol Hepatol. 2023-4

[7]
The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Immunity. 2023-2-14

[8]
Active eosinophils regulate host defence and immune responses in colitis.

Nature. 2023-3

[9]
B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing.

Immunity. 2022-12-13

[10]
Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn's Disease.

Inflamm Bowel Dis. 2023-2-1

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