Metabolic Changes Associated with Cardiomyocyte Dedifferentiation Enable Adult ammalian Cardiac Regeneration

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Title:	Metabolic Changes Associated with Cardiomyocyte Dedifferentiation Enable Adult ammalian Cardiac Regeneration
Authors:	鄭媛元 Yuan-Yuan Cheng, PhD, Zachery Gregorich, PhD, Ray P. Prajnamitra, PhD, David J. Lundy, PhD, Ting-Yun Ma, BS, Yu-Hsuan Huang, BS, Yi-Chan Lee, MS, Shu-Chian Ruan, BS, Jen-Hao Lin, MS, Po-Ju Lin, MS, Chiung-Wen Kuo, PhD, Peilin Chen, PhD, Yu-Ting Yan, PhD, Rong Tian, MD, PhD, Timothy J. Kamp, MD, PhD and Patrick C.H. Hsieh, MD, PhD
Contributors:	細胞治療與再生醫學國際博士學位學程
Date:	2022-11
Issue Date:	2025-03-28 10:24:53 (UTC+8)
Abstract:	Abstract Background: Cardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes (CMs). However, certain animals readily regenerate lost myocardium through a process involving dedifferentiation, which unlocks their proliferative capacities. Methods: We bred mice with inducible, CM-specific expression of the Yamanaka factors, enabling adult CM reprogramming and dedifferentiation in vivo. Results: Two days after induction, adult CMs presented a dedifferentiated phenotype and increased proliferation in vivo. Microarray analysis revealed that upregulation of ketogenesis was central to this process. Adeno-associated virus-driven HMGCS2 overexpression induced ketogenesis in adult CMs and recapitulated CM dedifferentiation and proliferation observed during partial reprogramming. This same phenomenon was found to occur after myocardial infarction, specifically in the border zone tissue, and HMGCS2 knockout mice showed impaired cardiac function and response to injury. Finally, we showed that exogenous HMGCS2 rescues cardiac function after ischemic injury. Conclusions: Our data demonstrate the importance of HMGCS2-induced ketogenesis as a means to regulate metabolic response to CM injury, thus allowing cell dedifferentiation and proliferation as a regenerative response.
Relation:	Circulation, Volume 146, Number 25
Description:	【112 新聘】臺北醫學大學教師升等專門著作職別：專任送審等級：助理教授著作送審
Data Type:	article
Appears in Collections:	[Scholarly output for promotion] 112 [International Ph.D. Program for Cell Therapy and Regeneration Medicine] article

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