In vivo partial cellular reprogramming enhances liver plasticity and regeneration.

Autor:	Hishida T; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shitibancho, Wakayama, Wakayama 640-8156, Japan., Yamamoto M; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Hishida-Nozaki Y; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Shao C; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Huang L; Razavi Newman Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Wang C; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Shojima K; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Xue Y; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Hang Y; Razavi Newman Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Shokhirev M; Razavi Newman Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Memczak S; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Sahu SK; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Hatanaka F; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Ros RR; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, Nº 135 12, 30107 Guadalupe, Spain., Maxwell MB; Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Division of Biological Sciences, UCSD, La Jolla, CA 92037, USA., Chavez J; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Shao Y; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Liao HK; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Martinez-Redondo P; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Guillen-Guillen I; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Hernandez-Benitez R; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Esteban CR; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA., Qu J; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China., Holmes MC; Ambys Medicines, 131 Oyster Point Boulevard, Suite 200, South San Francisco, CA 94080, USA., Yi F; Ambys Medicines, 131 Oyster Point Boulevard, Suite 200, South San Francisco, CA 94080, USA., Hickey RD; Ambys Medicines, 131 Oyster Point Boulevard, Suite 200, South San Francisco, CA 94080, USA., Garcia PG; Clinica CEMTRO, 28035 Madrid, Spain., Delicado EN; Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, Nº 135 12, 30107 Guadalupe, Spain., Castells A; Hospital Clinic of Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain., Campistol JM; Hospital Clinic of Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain., Yu Y; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Hargreaves DC; Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Asai A; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA., Reddy P; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Liu GH; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China., Izpisua Belmonte JC; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, San Diego, CA 92121, USA. Electronic address: jcbelmonte@altoslabs.com.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Apr 26; Vol. 39 (4), pp. 110730.
DOI:	10.1016/j.celrep.2022.110730
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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