It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
After birth, cardiomyocytes (CM) acquire numerous adaptations in order to efficiently pump blood throughout an animal’s lifespan. How this maturation process is regulated and coordinated is poorly understood. Here, we perform a CRISPR/Cas9 screen in mice and identify serum response factor (SRF) as a key regulator of CM maturation. Mosaic SRF depletion in neonatal CMs disrupts many aspects of their maturation, including sarcomere expansion, mitochondrial biogenesis, transverse-tubule formation, and cellular hypertrophy. Maintenance of maturity in adult CMs is less dependent on SRF. This stage-specific activity is associated with developmentally regulated SRF chromatin occupancy and transcriptional regulation. SRF directly activates genes that regulate sarcomere assembly and mitochondrial dynamics. Perturbation of sarcomere assembly but not mitochondrial dynamics recapitulates SRF knockout phenotypes. SRF overexpression also perturbs CM maturation. Together, these data indicate that carefully balanced SRF activity is essential to promote CM maturation through a hierarchy of cellular processes orchestrated by sarcomere assembly.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details








1 Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA
2 Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA; Department of Biology, Boston University, Boston, MA, USA
3 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
4 Department of Genetics, Harvard Medical School, Boston, MA, USA; Radcliffe Department of Medicine and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
5 Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA; Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
6 Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
7 Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA; Wenzhou Medical University, School of Life Sciences, Wenzhou, China
8 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
9 Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA; Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, College of Life Sciences, Hubei University, Wuhan, China
10 Department of Genetics, Harvard Medical School, Boston, MA, USA; Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA
11 Department of Genetics, Harvard Medical School, Boston, MA, USA
12 Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA