文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

创伤愈合可塑性使结肠炎中的祖细胞克隆扩增。

Wound-healing plasticity enables clonal expansion of founder progenitor cells in colitis.

机构信息

Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.

出版信息

Dev Cell. 2023 Nov 6;58(21):2309-2325.e7. doi: 10.1016/j.devcel.2023.08.011. Epub 2023 Aug 30.


DOI:10.1016/j.devcel.2023.08.011
PMID:37652012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10872951/
Abstract

Chronic colonic injury and inflammation pose high risks for field cancerization, wherein injury-associated mutations promote stem cell fitness and gradual clonal expansion. However, the long-term stability of some colitis-associated mutational fields could suggest alternate origins. Here, studies of acute murine colitis reveal a punctuated mechanism of massive, neutral clonal expansion during normal wound healing. Through three-dimensional (3D) imaging, quantitative fate mapping, and single-cell transcriptomics, we show that epithelial wound repair begins with the loss of structural constraints on regeneration, forming fused labyrinthine channels containing epithelial cells reprogrammed to a non-proliferative plastic state. A small but highly proliferative set of epithelial founder progenitor cells (FPCs) subsequently emerges and undergoes extensive cell division, enabling fluid-like lineage mixing and spreading across the colonic surface. Crypt budding restores the glandular organization, imprinting the pattern of clonal expansion. The emergence and functions of FPCs within a critical window of plasticity represent regenerative targets with implications for preneoplasia.

摘要

慢性结肠损伤和炎症会导致高风险的“场癌变”,其中损伤相关的突变会促进干细胞适应性和逐渐的克隆扩增。然而,一些结肠炎相关突变场的长期稳定性可能暗示了其他起源。在这里,对急性小鼠结肠炎的研究揭示了在正常伤口愈合过程中大量中性克隆扩增的间歇性机制。通过三维(3D)成像、定量命运图谱和单细胞转录组学,我们发现上皮伤口修复始于对再生结构约束的丧失,形成包含上皮细胞的融合迷宫状通道,这些上皮细胞被重新编程为非增殖性的可塑性状态。随后出现一小部分但具有高度增殖能力的上皮创始祖细胞(FPC),并经历广泛的细胞分裂,从而实现类似流体的谱系混合和在结肠表面的扩散。隐窝芽生恢复了腺体组织,印迹了克隆扩增的模式。在可塑性的关键窗口期内,FPC 的出现和功能代表了具有癌前病变意义的再生靶标。

相似文献

[1]
Wound-healing plasticity enables clonal expansion of founder progenitor cells in colitis.

Dev Cell. 2023-11-6

[2]
Transitional Anal Cells Mediate Colonic Re-epithelialization in Colitis.

Gastroenterology. 2022-6

[3]
Persistence of Lgr5+ colonic epithelial stem cells in mouse models of inflammatory bowel disease.

Am J Physiol Gastrointest Liver Physiol. 2021-9-1

[4]
Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease.

Gastroenterology. 2017-3-23

[5]
Atoh1 secretory progenitors possess renewal capacity independent of Lgr5 cells during colonic regeneration.

EMBO J. 2019-1-11

[6]
Recombinant soluble thrombomodulin accelerates epithelial stem cell proliferation in mouse intestinal organoids and promotes the mucosal healing in colitis.

J Gastroenterol Hepatol. 2021-11

[7]
Notoginsenoside R1 promotes Lgr5 stem cell and epithelium renovation in colitis mice via activating Wnt/β-Catenin signaling.

Acta Pharmacol Sin. 2024-7

[8]
The tyrosine phosphatase Shp-2 confers resistance to colonic inflammation by driving goblet cell function and crypt regeneration.

J Pathol. 2018-12-5

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

Immunity. 2022-12-13

[10]
Deficiency of Protein Tyrosine Phosphatase Non-Receptor Type 2 in Intestinal Epithelial Cells Has No Appreciable Impact on Dextran Sulphate Sodium Colitis Severity But Promotes Wound Healing.

Digestion. 2016

引用本文的文献

[1]
Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis.

Mucosal Immunol. 2025-2

[2]
Intestinal organoids to model Salmonella infection and its impact on progenitors.

Sci Rep. 2024-7-2

[3]
Myeloid Cell-Derived IL-1 Signaling Damps Neuregulin-1 from Fibroblasts to Suppress Colitis-Induced Early Repair of the Intestinal Epithelium.

Int J Mol Sci. 2024-4-18

[4]
The Past and Future of Inflammation as a Target to Cancer Prevention.

Cancer Prev Res (Phila). 2024-4-2

[5]
Colitis-induced upregulation of tumor necrosis factor receptor-2 (TNFR2) terminates epithelial regenerative signaling to restore homeostasis.

iScience. 2023-9-4

本文引用的文献

[1]
Transitional Anal Cells Mediate Colonic Re-epithelialization in Colitis.

Gastroenterology. 2022-6

[2]
Adaptive differentiation promotes intestinal villus recovery.

Dev Cell. 2022-1-24

[3]
Persistence of Lgr5+ colonic epithelial stem cells in mouse models of inflammatory bowel disease.

Am J Physiol Gastrointest Liver Physiol. 2021-9-1

[4]
Epithelial wound healing in inflammatory bowel diseases: the next therapeutic frontier.

Transl Res. 2021-10

[5]
Apc-mutant cells act as supercompetitors in intestinal tumour initiation.

Nature. 2021-6

[6]
Tracing oncogene-driven remodelling of the intestinal stem cell niche.

Nature. 2021-6

[7]
NOTUM from Apc-mutant cells biases clonal competition to initiate cancer.

Nature. 2021-6

[8]
Critical role of interferons in gastrointestinal injury repair.

Nat Commun. 2021-5-11

[9]
Clonal expansion in non-cancer tissues.

Nat Rev Cancer. 2021-4

[10]
Tissue regeneration: Reserve or reverse?

Science. 2021-2-19

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索