Age-associated H3K9me2 loss alters the regenerative equilibrium between murine lung alveolar and bronchiolar progenitors.

Autor:	Rowbotham SP; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: srowbotham@mgh.harvard.edu., Pessina P; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Garcia-de-Alba C; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Jensen J; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Nguyen Y; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Yoon J; Harvard Chan Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115., Li J; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Wong IG; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Fahey C; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Moye AL; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Chongsaritsinsuk J; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Bronson R; Rodent Histopathology Core, Harvard Medical School, Boston, MA 02115, USA., Ho Sui SJ; Harvard Chan Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115., Kim CF; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: carla.kim@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2023 Dec 18; Vol. 58 (24), pp. 2974-2991.e6. Date of Electronic Publication: 2023 Nov 16.
DOI:	10.1016/j.devcel.2023.10.011
Abstrakt:	The lung contains multiple progenitor cell types, but how their responses are choreographed during injury repair and whether this changes with age is poorly understood. We report that histone H3 lysine 9 di-methylation (H3K9me2), mediated by the methyltransferase G9a, regulates the dynamics of distal lung epithelial progenitor cells and that this regulation deteriorates with age. In aged mouse lungs, H3K9me2 loss coincided with fewer alveolar type 2 (AT2) cell progenitors and reduced alveolar regeneration but increased the frequency and activity of multipotent bronchioalveolar stem cells (BASCs) and bronchiolar progenitor club cells. H3K9me2 depletion in young mice decreased AT2 progenitor activity and impaired alveolar injury repair. Conversely, H3K9me2 depletion increased chromatin accessibility of bronchiolar cell genes, increased BASC frequency, and accelerated bronchiolar cell injury repair. These findings indicate that during aging, the epigenetic regulation that coordinates lung progenitor cells' regenerative responses becomes dysregulated, aiding our understanding of age-related susceptibility to lung disease. Competing Interests: Declaration of interests C.F.K. had a sponsored research agreement with Celgene/BMS Corporation during part of the period of these studies, yet the work in that agreement did not overlap with this study. C.F.K. and S.P.R. have a patent related to this work. C.F.K. and A.L.M. are founders of Cellforma. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu