دورية أكاديمية
β-Catenin drives distinct transcriptional networks in proliferative and nonproliferative cardiomyocytes.
| العنوان: | β-Catenin drives distinct transcriptional networks in proliferative and nonproliferative cardiomyocytes. |
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| المؤلفون: | Quaife-Ryan GA; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.; School of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia., Mills RJ; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia., Lavers G; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia., Voges HK; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria 3052, Australia., Vivien CJ; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria 3052, Australia., Elliott DA; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria 3052, Australia.; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.; Department of Paediatrics, The Royal Children's Hospital, University of Melbourne, Parkville, Victoria 3052, Australia., Ramialison M; Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia., Hudson JE; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia enzo.porrello@mcri.edu.au james.hudson@qimrberghofer.edu.au., Porrello ER; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria 3052, Australia enzo.porrello@mcri.edu.au james.hudson@qimrberghofer.edu.au.; Department of Physiology, School of Biomedical Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia. |
| المصدر: | Development (Cambridge, England) [Development] 2020 Nov 30; Vol. 147 (22). Date of Electronic Publication: 2020 Nov 30. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Company Of Biologists Limited Country of Publication: England NLM ID: 8701744 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-9129 (Electronic) Linking ISSN: 09501991 NLM ISO Abbreviation: Development Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge Eng : Company Of Biologists Limited Original Publication: [Cambridge] : Company of Biologists, [c1987- |
| مواضيع طبية MeSH: | Cell Proliferation* , Gene Regulatory Networks* , Transcription, Genetic* , Wnt Signaling Pathway*, Myocytes, Cardiac/*metabolism , beta Catenin/*metabolism, Animals ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Myocytes, Cardiac/cytology ; beta Catenin/genetics |
| مستخلص: | The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. By contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms for the developmental loss of cardiac regenerative capacity in mammals are not fully understood. Wnt/β-catenin signalling has been proposed as a key cardioregenerative pathway driving cardiomyocyte proliferation. Here, we show that Wnt/β-catenin signalling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro By contrast, Wnt/β-catenin signalling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling and chromatin immunoprecipitation sequencing of neonatal mouse and hPSC-CMs revealed a core Wnt/β-catenin-dependent transcriptional network governing cardiomyocyte proliferation. By contrast, β-catenin failed to re-engage this neonatal proliferative gene network in the adult heart despite partial transcriptional re-activation of a neonatal glycolytic gene programme. These findings suggest that β-catenin might be repurposed from regenerative to protective functions in the adult heart in a developmental process dependent on the metabolic status of cardiomyocytes. Competing Interests: Competing interestsG.A.Q.-R., R.J.M., J.E.H. and E.R.P. are co-inventors on patents for hCO maturation and cardiac regeneration held by The University of Queensland and QIMR Berghofer Medical Research Institute. J.E.H. is a co-inventor on licensed patents held by the University of Goettingen. R.J.M., E.R.P. and J.E.H. are co-founders, scientific advisors and stockholders in Dynomics. (© 2020. Published by The Company of Biologists Ltd.) |
| فهرسة مساهمة: | Keywords: Cardiac regeneration; Cardiomyocyte proliferation; Metabolism; Transcriptional regulation; Wnt/β-catenin |
| المشرفين على المادة: | 0 (beta Catenin) |
| تواريخ الأحداث: | Date Created: 20201104 Date Completed: 20210119 Latest Revision: 20220815 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1242/dev.193417 |
| PMID: | 33144401 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9129 |
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| DOI: | 10.1242/dev.193417 |