In vivo partial cellular reprogramming enhances liver plasticity and regeneration
| Autor: | 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, Ros, Ruben Rabadan, Maxwell, Matthew B, Chavez, Jasmine, Shao, Yanjiao, Liao, Hsin-Kai, Martinez-Redondo, Paloma, Guillen-Guillen, Isabel, Hernandez-Benitez, Reyna, Esteban, Concepcion Rodriguez, Qu, Jing, Holmes, Michael C, Yi, Fei, Hickey, Raymond D, Garcia, Pedro Guillen, Delicado, Estrella Nuñez, Castells, Antoni, Campistol, Josep M, Yu, Yang, Hargreaves, Diana C, Asai, Akihiro, Reddy, Pradeep, Liu, Guang-Hui, Izpisua Belmonte, Juan Carlos |
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| Rok vydání: | 2022 |
| Předmět: |
Mammals
Stem cell research [CP] 5.2 Cellular and gene therapies Liver Disease dedifferentiation Chronic Liver Disease and Cirrhosis Medical Physiology reprogramming Cell Dedifferentiation Cellular Reprogramming liver Stem Cell Research Regenerative Medicine Oral and gastrointestinal Liver Regeneration Mice Liver regeneration Hepatocytes Animals Stem Cell Research - Nonembryonic - Non-Human Biochemistry and Cell Biology Development of treatments and therapeutic interventions Digestive Diseases |
| Zdroj: | Cell reports, vol 39, iss 4 |
| Popis: | 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 invivo 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 invivo induces cellular plasticity and counteracts liver failure, suggesting that partial reprogramming may represent an avenue for enhancing tissue regeneration. |
| Databáze: | OpenAIRE |
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