Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver
The adult liver has an exceptional ability to regenerate, but how it maintains its specialized functions during regeneration is unclear. Here, we used partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ∼22,000 liver cells through...
| Autores: | , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/115642 |
| Acceso en línea: | https://hdl.handle.net/10171/115642 |
| Access Level: | acceso abierto |
| Palabra clave: | Adult liver Regenerate Hepatectomy |
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Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liverChembazhi, U.V. (Ullas V.)|||/items/0b76f56a-ed66-41f3-9bcd-e546a7a147f1Bangru, S. (Sushant)|||/items/f340e0bb-f0b9-455b-8c99-8e8784e48bc2Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5aKalsotra, A. (Auinash)|||/items/4de433f6-3a60-43f7-ad10-0d1524b66cdfAdult liverRegenerateHepatectomyThe adult liver has an exceptional ability to regenerate, but how it maintains its specialized functions during regeneration is unclear. Here, we used partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ∼22,000 liver cells through the initiation, progression, and termination phases of mouse liver regeneration. Our results uncovered that, following PHx, a subset of hepatocytes transiently reactivates an early-postnatal-like gene expression program to proliferate, while a distinct population of metabolically hyperactive cells appears to compensate for any temporary deficits in liver function. Cumulative EdU labeling and immunostaining of metabolic, portal, and central vein-specific markers revealed that hepatocyte proliferation after PHx initiates in the midlobular region before proceeding toward the periportal and pericentral areas. We further demonstrate that portal and central vein proximal hepatocytes retain their metabolically active state to preserve essential liver functions while midlobular cells proliferate nearby. Through combined analysis of gene regulatory networks and cell-cell interaction maps, we found that regenerating hepatocytes redeploy key developmental regulons, which are guided by extensive ligand-receptor-mediated signaling events between hepatocytes and nonparenchymal cells. Altogether, our study offers a detailed blueprint of the intercellular crosstalk and cellular reprogramming that balances the metabolic and proliferative requirements of a regenerating liver.Cold Spring Harbor Laboratory PressDadun. Depósito Académico Digital Universidad de Navarra20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/115642reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1156422026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| title |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| spellingShingle |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver Chembazhi, U.V. (Ullas V.)|||/items/0b76f56a-ed66-41f3-9bcd-e546a7a147f1 Adult liver Regenerate Hepatectomy |
| title_short |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| title_full |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| title_fullStr |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| title_full_unstemmed |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| title_sort |
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver |
| dc.creator.none.fl_str_mv |
Chembazhi, U.V. (Ullas V.)|||/items/0b76f56a-ed66-41f3-9bcd-e546a7a147f1 Bangru, S. (Sushant)|||/items/f340e0bb-f0b9-455b-8c99-8e8784e48bc2 Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Kalsotra, A. (Auinash)|||/items/4de433f6-3a60-43f7-ad10-0d1524b66cdf |
| author |
Chembazhi, U.V. (Ullas V.)|||/items/0b76f56a-ed66-41f3-9bcd-e546a7a147f1 |
| author_facet |
Chembazhi, U.V. (Ullas V.)|||/items/0b76f56a-ed66-41f3-9bcd-e546a7a147f1 Bangru, S. (Sushant)|||/items/f340e0bb-f0b9-455b-8c99-8e8784e48bc2 Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Kalsotra, A. (Auinash)|||/items/4de433f6-3a60-43f7-ad10-0d1524b66cdf |
| author_role |
author |
| author2 |
Bangru, S. (Sushant)|||/items/f340e0bb-f0b9-455b-8c99-8e8784e48bc2 Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Kalsotra, A. (Auinash)|||/items/4de433f6-3a60-43f7-ad10-0d1524b66cdf |
| author2_role |
author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Adult liver Regenerate Hepatectomy |
| topic |
Adult liver Regenerate Hepatectomy |
| description |
The adult liver has an exceptional ability to regenerate, but how it maintains its specialized functions during regeneration is unclear. Here, we used partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ∼22,000 liver cells through the initiation, progression, and termination phases of mouse liver regeneration. Our results uncovered that, following PHx, a subset of hepatocytes transiently reactivates an early-postnatal-like gene expression program to proliferate, while a distinct population of metabolically hyperactive cells appears to compensate for any temporary deficits in liver function. Cumulative EdU labeling and immunostaining of metabolic, portal, and central vein-specific markers revealed that hepatocyte proliferation after PHx initiates in the midlobular region before proceeding toward the periportal and pericentral areas. We further demonstrate that portal and central vein proximal hepatocytes retain their metabolically active state to preserve essential liver functions while midlobular cells proliferate nearby. Through combined analysis of gene regulatory networks and cell-cell interaction maps, we found that regenerating hepatocytes redeploy key developmental regulons, which are guided by extensive ligand-receptor-mediated signaling events between hepatocytes and nonparenchymal cells. Altogether, our study offers a detailed blueprint of the intercellular crosstalk and cellular reprogramming that balances the metabolic and proliferative requirements of a regenerating liver. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2021-01-01 2021 2021-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/115642 |
| url |
https://hdl.handle.net/10171/115642 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Cold Spring Harbor Laboratory Press |
| publisher.none.fl_str_mv |
Cold Spring Harbor Laboratory Press |
| dc.source.none.fl_str_mv |
reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
| reponame_str |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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15,812429 |