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Identification of stem cells in small intestine and colon by marker gene Lgr5

Author

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  • Nick Barker

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Johan H. van Es

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Jeroen Kuipers

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Pekka Kujala

    (The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Maaike van den Born

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Miranda Cozijnsen

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Andrea Haegebarth

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Jeroen Korving

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Harry Begthel

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

  • Peter J. Peters

    (The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Hans Clevers

    (Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands)

Abstract

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.

Suggested Citation

  • Nick Barker & Johan H. van Es & Jeroen Kuipers & Pekka Kujala & Maaike van den Born & Miranda Cozijnsen & Andrea Haegebarth & Jeroen Korving & Harry Begthel & Peter J. Peters & Hans Clevers, 2007. "Identification of stem cells in small intestine and colon by marker gene Lgr5," Nature, Nature, vol. 449(7165), pages 1003-1007, October.
    • Handle: RePEc:nat:nature:v:449:y:2007:i:7165:d:10.1038_nature06196
    DOI: 10.1038/nature06196
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    1. Yadong Qi & Jiamin He & Yawen Zhang & Qiwei Ge & Qiwen Wang & Luyi Chen & Jilei Xu & Lan Wang & Xueqin Chen & Dingjiacheng Jia & Yifeng Lin & Chaochao Xu & Ying Zhang & Tongyao Hou & Jianmin Si & Shuj, 2023. "Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Tsunaki Higa & Yasutaka Okita & Akinobu Matsumoto & Shogo Nakayama & Takeru Oka & Osamu Sugahara & Daisuke Koga & Shoichiro Takeishi & Hirokazu Nakatsumi & Naoki Hosen & Sylvie Robine & Makoto M. Take, 2022. "Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Alfredo Erazo-Oliveras & Mónica Muñoz-Vega & Mohamed Mlih & Venkataramana Thiriveedi & Michael L. Salinas & Jaileen M. Rivera-Rodríguez & Eunjoo Kim & Rachel C. Wright & Xiaoli Wang & Kerstin K. Landr, 2023. "Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    4. Adrian On Wah Leung & Andrew Chung Hin Poon & Xue Wang & Chen Feng & Peikai Chen & Zhengfan Zheng & Michael KaiTsun To & Wilson Cheuk Wing Chan & Martin Cheung & Danny Chan, 2024. "Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Yael Korem & Pablo Szekely & Yuval Hart & Hila Sheftel & Jean Hausser & Avi Mayo & Michael E Rothenberg & Tomer Kalisky & Uri Alon, 2015. "Geometry of the Gene Expression Space of Individual Cells," PLOS Computational Biology, Public Library of Science, vol. 11(7), pages 1-27, July.
    6. Joana Silva & Ferhat Alkan & Sofia Ramalho & Goda Snieckute & Stefan Prekovic & Ana Krotenberg Garcia & Santiago Hernández-Pérez & Rob Kammen & Danielle Barnum & Liesbeth Hoekman & Maarten Altelaar & , 2022. "Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Jeremiah Bernier-Latmani & Cristina Mauri & Rachel Marcone & François Renevey & Stephan Durot & Liqun He & Michael Vanlandewijck & Catherine Maclachlan & Suzel Davanture & Nicola Zamboni & Graham W. K, 2022. "ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Peter Bailey & Rachel A. Ridgway & Patrizia Cammareri & Mairi Treanor-Taylor & Ulla-Maja Bailey & Christina Schoenherr & Max Bone & Daniel Schreyer & Karin Purdie & Jason Thomson & William Rickaby & R, 2023. "Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Shuting Li & Chia-Wen Lu & Elia C. Diem & Wang Li & Melanie Guderian & Marc Lindenberg & Friederike Kruse & Manuela Buettner & Stefan Floess & Markus R. Winny & Robert Geffers & Hans-Hermann Richnow &, 2022. "Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5+ intestinal stem cell function," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Philip S. Robinson & Laura E. Thomas & Federico Abascal & Hyunchul Jung & Luke M. R. Harvey & Hannah D. West & Sigurgeir Olafsson & Bernard C. H. Lee & Tim H. H. Coorens & Henry Lee-Six & Laura Butlin, 2022. "Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Jong Hoon Won & Jacob S. Choi & Joon-Il Jun, 2022. "CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Qing Chen & Xin Zhang & Wei-Min Li & Yu-Qiang Ji & Hao-Zhe Cao & Pengsheng Zheng, 2014. "Prognostic Value of LGR5 in Colorectal Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-9, September.
    13. Elisa Manieri & Guodong Tie & Ermanno Malagola & Davide Seruggia & Shariq Madha & Adrianna Maglieri & Kun Huang & Yuko Fujiwara & Kevin Zhang & Stuart H. Orkin & Timothy C. Wang & Ruiyang He & Neil Mc, 2023. "Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Shamir Montazid & Sheila Bandyopadhyay & Daniel W. Hart & Nan Gao & Brian Johnson & Sri G. Thrumurthy & Dustin J. Penn & Bettina Wernisch & Mukesh Bansal & Philipp M. Altrock & Fabian Rost & Patrycja , 2023. "Adult stem cell activity in naked mole rats for long-term tissue maintenance," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    15. Lana Kostic & Carly Leung & Katzrin Ahmad Murad & Snezhina Kancheva & Stefano Perna & Bernett Lee & Nick Barker, 2024. "Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    16. Marta Kapalczynska & Manqiang Lin & Jeroen Maertzdorf & Julian Heuberger & Stefanie Muellerke & Xiangsheng Zuo & Ramon Vidal & Imad Shureiqi & Anne-Sophie Fischer & Sascha Sauer & Hilmar Berger & Evel, 2022. "BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Adam E. Hall & Sebastian Öther-Gee Pohl & Patrizia Cammareri & Stuart Aitken & Nicholas T. Younger & Michela Raponi & Caroline V. Billard & Alfonso Bolado Carrancio & Aslihan Bastem & Paz Freile & Fio, 2022. "RNA splicing is a key mediator of tumour cell plasticity and a therapeutic vulnerability in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Marco Calafiore & Ya-Yuan Fu & Paola Vinci & Viktor Arnhold & Winston Y. Chang & Suze A. Jansen & Anastasiya Egorova & Shuichiro Takashima & Jason Kuttiyara & Takahiro Ito & Jonathan Serody & Susumu N, 2023. "A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    19. Clara Morral & Arshad Ayyaz & Hsuan-Cheng Kuo & Mardi Fink & Ioannis I. Verginadis & Andrea R. Daniel & Danielle N. Burner & Lucy M. Driver & Sloane Satow & Stephanie Hasapis & Reem Ghinnagow & Lixia , 2024. "p53 promotes revival stem cells in the regenerating intestine after severe radiation injury," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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