Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus

The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing...

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Main Authors: Kostic, Lana, Leung, Carly, Murad, Katzrin Ahmad, Kancheva, Snezhina, Perna, Stefano, Lee, Bernett, Barker, Nick
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/181252
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1812522024-11-24T15:39:28Z Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus Kostic, Lana Leung, Carly Murad, Katzrin Ahmad Kancheva, Snezhina Perna, Stefano Lee, Bernett Barker, Nick Lee Kong Chian School of Medicine (LKCMedicine) Singapore Immunology Network, A*STAR Infectious Disease Labs, A*STAR Khoo Teck Puat Hospital Centre for Biomedical Informatics Medicine, Health and Life Sciences Epithelium cell Esophagus muscle The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This research is supported by the Agency for Science, Technology and Research (A*STAR) and the National Research Foundation (NRF) NRFI2017-03. 2024-11-19T04:44:56Z 2024-11-19T04:44:56Z 2024 Journal Article Kostic, L., Leung, C., Murad, K. A., Kancheva, S., Perna, S., Lee, B. & Barker, N. (2024). Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus. Nature Communications, 15(1), 7145-. https://dx.doi.org/10.1038/s41467-024-51559-4 2041-1723 https://hdl.handle.net/10356/181252 10.1038/s41467-024-51559-4 39164270 2-s2.0-85201669921 1 15 7145 en NRFI2017-03 Nature Communications © 2024 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
Epithelium cell
Esophagus muscle
spellingShingle Medicine, Health and Life Sciences
Epithelium cell
Esophagus muscle
Kostic, Lana
Leung, Carly
Murad, Katzrin Ahmad
Kancheva, Snezhina
Perna, Stefano
Lee, Bernett
Barker, Nick
Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
description The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Kostic, Lana
Leung, Carly
Murad, Katzrin Ahmad
Kancheva, Snezhina
Perna, Stefano
Lee, Bernett
Barker, Nick
format Article
author Kostic, Lana
Leung, Carly
Murad, Katzrin Ahmad
Kancheva, Snezhina
Perna, Stefano
Lee, Bernett
Barker, Nick
author_sort Kostic, Lana
title Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
title_short Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
title_full Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
title_fullStr Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
title_full_unstemmed Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
title_sort lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus
publishDate 2024
url https://hdl.handle.net/10356/181252
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