• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
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
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
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 @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

驱动结直肠癌的发生和抑制其在结肠发育过程中的增殖。

drives cryptogenesis and restrains proliferation during colon development.

机构信息

Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States.

Department of Biology, University of Oregon, Eugene, Oregon, United States.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2023 Dec 1;325(6):G570-G581. doi: 10.1152/ajpgi.00094.2023. Epub 2023 Oct 24.

DOI:10.1152/ajpgi.00094.2023
PMID:37873577
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11192189/
Abstract

Growth and specification of the mouse intestine occurs in utero and concludes after birth. Although numerous studies have examined this developmental process in the small intestine, far less is known about the cellular and molecular cues required for colon development. In this study, we examine the morphological events leading to crypt formation, epithelial cell differentiation, proliferation, and the emergence and expression of a stem and progenitor cell marker Lrig1. Through multicolor lineage tracing, we show Lrig1-expressing cells are present at birth and behave as stem cells to establish clonal crypts within 3 wk of life. In addition, we use an inducible knockout mouse to eliminate and show restrains proliferation within a critical developmental time window, without impacting colonic epithelial cell differentiation. Our study illustrates morphological changes during crypt development and the importance of Lrig1 in the developing colon. Our studies define the importance of studying Lrig1 in colon development. We address a critical gap in the intestinal development literature and provide new information about the molecular cues that guide colon development. Using a novel, inducible knockout of , we show Lrig1 is required for appropriate colon epithelial growth and illustrate the importance of Lrig1-expressing cells in the establishment of colonic crypts.

摘要

小鼠肠道的生长和特化发生在子宫内,并在出生后结束。尽管许多研究已经检查了小肠的这个发育过程,但对于大肠发育所需的细胞和分子线索知之甚少。在这项研究中,我们检查了导致隐窝形成、上皮细胞分化、增殖以及出现和表达干细胞和祖细胞标记物 Lrig1 的形态事件。通过多色谱系追踪,我们发现在出生时就存在表达 Lrig1 的细胞,并且作为干细胞在生命的头 3 周内建立克隆隐窝。此外,我们使用诱导型敲除小鼠消除 ,并表明 在关键的发育时间窗口内限制增殖,而不影响结肠上皮细胞分化。我们的研究说明了隐窝发育过程中的形态变化以及 Lrig1 在发育中的结肠中的重要性。我们的研究阐明了研究 Lrig1 在结肠发育中的重要性。我们解决了肠道发育文献中的一个关键空白,并提供了有关指导结肠发育的分子线索的新信息。使用新型诱导型 的敲除,我们表明 Lrig1 是结肠上皮生长所必需的,并说明了表达 Lrig1 的细胞在结肠隐窝建立中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe2/11192189/8192eb826287/gi-00094-2023r01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe2/11192189/8192eb826287/gi-00094-2023r01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe2/11192189/8192eb826287/gi-00094-2023r01.jpg

相似文献

1
drives cryptogenesis and restrains proliferation during colon development.驱动结直肠癌的发生和抑制其在结肠发育过程中的增殖。
Am J Physiol Gastrointest Liver Physiol. 2023 Dec 1;325(6):G570-G581. doi: 10.1152/ajpgi.00094.2023. Epub 2023 Oct 24.
2
The Role of Lrig1 in the Development of the Colonic Epithelium.Lrig1在结肠上皮发育中的作用。
bioRxiv. 2023 May 2:2023.05.02.539114. doi: 10.1101/2023.05.02.539114.
3
The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor.pan-ErbB 阴性调节剂 Lrig1 是一种肠道干细胞标志物,具有肿瘤抑制作用。
Cell. 2012 Mar 30;149(1):146-58. doi: 10.1016/j.cell.2012.02.042.
4
Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach.Lrig1+ 胃峡部祖细胞在成年鼠胃损伤恢复过程中恢复正常胃谱系细胞。
Gut. 2018 Sep;67(9):1595-1605. doi: 10.1136/gutjnl-2017-313874. Epub 2017 Aug 16.
5
LRIG1 Regulates Ontogeny of Smooth Muscle-Derived Subsets of Interstitial Cells of Cajal in Mice.LRIG1调节小鼠中 Cajal 间质细胞平滑肌衍生亚群的个体发生。
Gastroenterology. 2015 Aug;149(2):407-19.e8. doi: 10.1053/j.gastro.2015.04.018. Epub 2015 Apr 25.
6
Targeted mobilization of Lrig1 gastric epithelial stem cell populations by a carcinogenic type IV secretion system.致癌型 IV 型分泌系统靶向动员 Lrig1 胃上皮干细胞群体。
Proc Natl Acad Sci U S A. 2019 Sep 24;116(39):19652-19658. doi: 10.1073/pnas.1903798116. Epub 2019 Sep 5.
7
Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis.Lrig1 表达祖细胞中一个 Apc 等位基因的诱导缺失导致具有家族性腺瘤性息肉病特征的多个远端结肠肿瘤。
Am J Physiol Gastrointest Liver Physiol. 2014 Jul 1;307(1):G16-23. doi: 10.1152/ajpgi.00358.2013. Epub 2014 May 15.
8
Targeted intestinal deletion of Rho guanine nucleotide exchange factor 7, βPIX, impairs enterocyte proliferation, villus maturation, and mucosal defenses in mice.靶向肠道 Rho 鸟苷酸交换因子 7(βPIX)缺失会损害小鼠肠上皮细胞增殖、绒毛成熟和黏膜防御。
Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1;320(4):G627-G643. doi: 10.1152/ajpgi.00415.2020. Epub 2021 Feb 10.
9
Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia.bcl-2在肠上皮中的差异表达。与结肠隐窝细胞凋亡减弱及结肠肿瘤发生率的相关性。
J Cell Sci. 1995 Jun;108 ( Pt 6):2261-71. doi: 10.1242/jcs.108.6.2261.
10
Lrig1 expression identifies quiescent stem cells in the ventricular-subventricular zone from postnatal development to adulthood and limits their persistent hyperproliferation.Lrig1 表达可识别出生后发育到成年时期脑室下区的静息干细胞,并限制其持续过度增殖。
Neural Dev. 2023 Jan 11;18(1):1. doi: 10.1186/s13064-022-00169-1.

引用本文的文献

1
The emerging role of intestinal stem cells in ulcerative colitis.肠道干细胞在溃疡性结肠炎中的新作用。
Front Med (Lausanne). 2025 Mar 25;12:1569328. doi: 10.3389/fmed.2025.1569328. eCollection 2025.

本文引用的文献

1
Organoid-based modeling of intestinal development, regeneration, and repair.基于类器官的肠道发育、再生和修复模型。
Cell Death Differ. 2021 Jan;28(1):95-107. doi: 10.1038/s41418-020-00665-z. Epub 2020 Nov 18.
2
Intestinal Morphogenesis in Development, Regeneration, and Disease: The Potential Utility of Intestinal Organoids for Studying Compartmentalization of the Crypt-Villus Structure.发育、再生及疾病中的肠道形态发生:肠道类器官在研究隐窝-绒毛结构分区中的潜在用途
Front Cell Dev Biol. 2020 Oct 23;8:593969. doi: 10.3389/fcell.2020.593969. eCollection 2020.
3
LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex.
LRIG1 通过抑制 EGF 受体信号调控神经前体细胞在大脑皮层中的增殖。
Cell Rep. 2020 Oct 13;33(2):108257. doi: 10.1016/j.celrep.2020.108257.
4
Mouse gastrulation: Coordination of tissue patterning, specification and diversification of cell fate.小鼠原肠胚形成:组织模式的协调、细胞命运的特化和多样化。
Mech Dev. 2020 Sep;163:103617. doi: 10.1016/j.mod.2020.103617. Epub 2020 May 27.
5
LGR5 controls extracellular matrix production by stem cells in the developing intestine.LGR5 控制着发育中肠道干细胞的细胞外基质产生。
EMBO Rep. 2020 Jul 3;21(7):e49224. doi: 10.15252/embr.201949224. Epub 2020 May 28.
6
The Villin1 Gene Promoter Drives Cre Recombinase Expression in Extraintestinal Tissues.维林1基因启动子驱动肠外组织中的Cre重组酶表达。
Cell Mol Gastroenterol Hepatol. 2020;10(4):864-867.e5. doi: 10.1016/j.jcmgh.2020.05.009. Epub 2020 May 25.
7
Lrig1 expression prospectively identifies stem cells in the ventricular-subventricular zone that are neurogenic throughout adult life.Lrig1 表达可前瞻性识别脑室下区中的干细胞,这些干细胞在成年期具有神经发生能力。
Neural Dev. 2020 Mar 17;15(1):3. doi: 10.1186/s13064-020-00139-5.
8
Hedgehog-Activated Fat4 and PCP Pathways Mediate Mesenchymal Cell Clustering and Villus Formation in Gut Development.Hedgehog 激活的 Fat4 和 PCP 通路介导线粒体细胞聚类和绒毛形成在肠道发育中。
Dev Cell. 2020 Mar 9;52(5):647-658.e6. doi: 10.1016/j.devcel.2020.02.003.
9
A direct comparison of mouse and human intestinal development using epithelial gene expression patterns.利用肠上皮基因表达模式对小鼠和人类肠道发育进行直接比较。
Pediatr Res. 2020 Jul;88(1):66-76. doi: 10.1038/s41390-019-0472-y. Epub 2019 Jun 26.
10
Mini-gut: a promising model for drug development.迷你肠道:药物研发的有前景模型。
Drug Discov Today. 2019 Sep;24(9):1784-1794. doi: 10.1016/j.drudis.2019.06.006. Epub 2019 Jun 15.