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2022-04-26

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cc-by (c) Hishida, T. et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/207808

In vivo partial cellular reprogramming enhances liver plasticity and regeneration.

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Recurs relacionat

https://doi.org/10.1016/j.celrep.2022.110730

Resum

Mammals have limited regenerative capacity, whereas some vertebrates, like fish and salamanders, are able to regenerate their organs efficiently. The regeneration in these species depends on cell dedifferentiation followed by proliferation. We generate a mouse model that enables the inducible expression of the four Yamanaka factors (Oct-3/4, Sox2, Klf4, and c-Myc, or 4F) specifically in hepatocytes. Transient in vivo 4F expression induces partial reprogramming of adult hepatocytes to a progenitor state and concomitantly increases cell proliferation. This is indicated by reduced expression of differentiated hepatic-lineage markers, an increase in markers of proliferation and chromatin modifiers, global changes in DNA accessibility, and an acquisition of liver stem and progenitor cell markers. Functionally, short-term expression of 4F enhances liver regenerative capacity through topoisomerase2-mediated partial reprogramming. Our results reveal that liver-specific 4F expression in vivo induces cellular plasticity and counteracts liver failure, suggesting that partial reprogramming may represent an avenue for enhancing tissue regeneration.

Matèries

Cèl·lules mare, Teràpia cel·lular, Metabolisme cel·lular, Mamífers, Fetge

Matèries (anglès)

Stem cells, Cellular therapy, Cell metabolism, Mammals, Liver

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Col·leccions

Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

HISHIDA, Tomoaki, YAMAMOTO, Mako, HISHIDA NOZAKI, Yuriko, SHAO, Changwei, HUANG, Ling, WANG, Chao, SHOJIMA, Kensaku, XUE, Yuan, HANG, Yuqing, SHOKHIREV, Maxim, MEMCZAK, Sebastian, SAHU, Sanjeeb kumar, HATANAKA, Fumiyuki, RABADÁN ROS, Rubén, MAXWELL, Matthew b., CHAVEZ, Jasmine, SHAO, Yanjiao, LIAO, Hsin-kai, MARTÍNEZ REDONDO, Paloma, GUILLEN GUILLEN, Isabel, HERNÁNDEZ BENÍTEZ, Reyna, RODRIGUEZ ESTEBAN, Concepción, QU, Jing, HOLMES, Michael c., YI, Fei, HICKEY, Raymond d., GUILLEN GARCIA, Pedro, NUÑEZ DELICADO, Estrella, CASTELLS GARANGOU, Antoni, CAMPISTOL PLANA, Josep m., YU, Yang, HARGREAVES, Diana c., ASAI, Akihiro, REDDY, Pradeep, LIU, Guang-hui, IZPISÚA BELMONTE, Juan carlos. In vivo partial cellular reprogramming enhances liver plasticity and regeneration.. _Cell Reports_. 2022. Vol. 39, núm. 4. [consulta: 24 de gener de 2026]. ISSN: 2211-1247. [Disponible a: https://hdl.handle.net/2445/207808]

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