Suppr超能文献

Lgr5 肠道干细胞具有较高的端粒酶活性,并随机分离其染色体。

Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes.

机构信息

Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.

出版信息

EMBO J. 2011 Mar 16;30(6):1104-9. doi: 10.1038/emboj.2011.26. Epub 2011 Feb 4.

Abstract

Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse, yet divide every day. We now demonstrate biochemically that primary isolated Lgr5+ve stem cells contain significant telomerase activity. Telomerase activity rapidly decreases in the undifferentiated progeny of these stem cells and is entirely lost in differentiated villus cells. Conversely, asymmetric segregation of chromosomes has been proposed as a mechanism for stem cells to protect their genomes against damage. We determined the average cell cycle length of Lgr5+ve stem cells at 21.5 h and find that Lgr5+ve intestinal stem cells randomly segregate newly synthesized DNA strands, opposing the 'immortal strand' hypothesis.

摘要

体细胞被认为其分裂次数是有限的。这种机制可以使干细胞保持完整性,预防疾病。然而,我们最近发现,肠道隐窝干细胞可以在老鼠的一生中持续存在,并且每天都在分裂。我们现在从生化角度证明,分离出来的原代 Lgr5+ve 干细胞含有大量端粒酶活性。端粒酶活性在这些干细胞的未分化后代中迅速下降,在分化的绒毛细胞中完全消失。相反,染色体的不对称分离被认为是干细胞保护基因组免受损伤的一种机制。我们确定 Lgr5+ve 干细胞的平均细胞周期长度为 21.5 小时,并且发现 Lgr5+ve 肠道干细胞随机分离新合成的 DNA 链,与“不朽链”假说相反。

相似文献

1
Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes.
EMBO J. 2011 Mar 16;30(6):1104-9. doi: 10.1038/emboj.2011.26. Epub 2011 Feb 4.
2
TRAPping telomerase within the intestinal stem cell niche.
EMBO J. 2011 Mar 16;30(6):986-7. doi: 10.1038/emboj.2011.51.
4
Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells.
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):179-84. doi: 10.1073/pnas.1013004108. Epub 2010 Dec 20.
5
Intestinal Epithelial Stem Cells: Distinct Behavior After Surgical Injury and Teduglutide Administration.
J Invest Surg. 2018 Jun;31(3):243-252. doi: 10.1080/08941939.2017.1294217. Epub 2017 Mar 31.
6
Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms.
Phys Rev E Stat Nonlin Soft Matter Phys. 2005 Apr;71(4 Pt 1):041914. doi: 10.1103/PhysRevE.71.041914. Epub 2005 Apr 27.
8
Primary Intestinal Epithelial Organoid Culture.
Methods Mol Biol. 2020;2171:185-200. doi: 10.1007/978-1-0716-0747-3_11.
9
Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions.
Carcinogenesis. 2015 Jan;36(1):25-31. doi: 10.1093/carcin/bgu221. Epub 2014 Oct 24.
10
Interplay between metabolic identities in the intestinal crypt supports stem cell function.
Nature. 2017 Mar 16;543(7645):424-427. doi: 10.1038/nature21673. Epub 2017 Mar 8.

引用本文的文献

1
Roles of intestinal stem cells in inflammatory bowel disease pathogenesis.
World J Stem Cells. 2025 Aug 26;17(8):107639. doi: 10.4252/wjsc.v17.i8.107639.
2
OpenEMMU: A versatile, open-source EdU multiplexing methodology for studying DNA replication and cell cycle dynamics.
iScience. 2025 Aug 16;28(9):113380. doi: 10.1016/j.isci.2025.113380. eCollection 2025 Sep 19.
4
Can Unicellular Organisms Sequester a Germline? The Yeast-Germline Hypothesis.
Bioessays. 2025 Jun;47(6):e70003. doi: 10.1002/bies.70003. Epub 2025 May 2.
5
Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.
Int J Mol Sci. 2024 Dec 14;25(24):13417. doi: 10.3390/ijms252413417.
7
Cellular and molecular mechanisms of asymmetric stem cell division in tissue homeostasis.
Genes Cells. 2024 Dec;29(12):1099-1110. doi: 10.1111/gtc.13172. Epub 2024 Oct 8.
9
Molecular mechanisms of aging and anti-aging strategies.
Cell Commun Signal. 2024 May 24;22(1):285. doi: 10.1186/s12964-024-01663-1.
10
Telomeres: Dysfunction, Maintenance, Aging and Cancer.
Aging Dis. 2023 Nov 29;15(6):2595-2631. doi: 10.14336/AD.2023.1128.

本文引用的文献

1
Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells.
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):179-84. doi: 10.1073/pnas.1013004108. Epub 2010 Dec 20.
2
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts.
Nature. 2011 Jan 20;469(7330):415-8. doi: 10.1038/nature09637. Epub 2010 Nov 28.
3
Intestinal stem cell replacement follows a pattern of neutral drift.
Science. 2010 Nov 5;330(6005):822-5. doi: 10.1126/science.1196236. Epub 2010 Sep 23.
5
Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue.
Cell Stem Cell. 2010 Feb 5;6(2):175-81. doi: 10.1016/j.stem.2009.12.007.
6
DNA damage response and cellular senescence in tissues of aging mice.
Aging Cell. 2009 Jun;8(3):311-23. doi: 10.1111/j.1474-9726.2009.00481.x. Epub 2009 Apr 9.
7
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
Nature. 2009 May 14;459(7244):262-5. doi: 10.1038/nature07935. Epub 2009 Mar 29.
8
Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine.
Gastroenterology. 2009 Jun;136(7):2187-2194.e1. doi: 10.1053/j.gastro.2009.03.002. Epub 2009 Mar 24.
9
The majority of multipotent epidermal stem cells do not protect their genome by asymmetrical chromosome segregation.
Stem Cells. 2008 Nov;26(11):2964-73. doi: 10.1634/stemcells.2008-0634. Epub 2008 Sep 4.
10
Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells.
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10420-5. doi: 10.1073/pnas.0804800105. Epub 2008 Jul 23.

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

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验