Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling
Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/15034 |
| _version_ | 1811199991055646720 |
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| author | Kenji Kamimoto Kota Kaneko Cindy Yuet-Yin Kok Hajime Okada Atsushi Miyajima Tohru Itoh |
| author_facet | Kenji Kamimoto Kota Kaneko Cindy Yuet-Yin Kok Hajime Okada Atsushi Miyajima Tohru Itoh |
| author_sort | Kenji Kamimoto |
| collection | DOAJ |
| description | Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. |
| first_indexed | 2024-04-12T01:57:20Z |
| format | Article |
| id | doaj.art-a429f21417f24e28b45e7f9abb1c0805 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:57:20Z |
| publishDate | 2016-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a429f21417f24e28b45e7f9abb1c08052022-12-22T03:52:46ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.15034Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodelingKenji Kamimoto0Kota Kaneko1Cindy Yuet-Yin Kok2Hajime Okada3Atsushi Miyajima4Tohru Itoh5https://orcid.org/0000-0002-6579-1638Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, JapanLaboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, JapanDynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity.https://elifesciences.org/articles/15034liver regenerationductular reaction3D imagingclonal analysismathematical modeling |
| spellingShingle | Kenji Kamimoto Kota Kaneko Cindy Yuet-Yin Kok Hajime Okada Atsushi Miyajima Tohru Itoh Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling eLife liver regeneration ductular reaction 3D imaging clonal analysis mathematical modeling |
| title | Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling |
| title_full | Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling |
| title_fullStr | Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling |
| title_full_unstemmed | Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling |
| title_short | Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling |
| title_sort | heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling |
| topic | liver regeneration ductular reaction 3D imaging clonal analysis mathematical modeling |
| url | https://elifesciences.org/articles/15034 |
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