Molecular Atlas of Postnatal Mouse Heart Development

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Talman , V , Teppo , J S , Pöhö , P A , Movahedi , P , Vaikkinen , A , Karhu , S T , Trošt , K , Suvitaival , T , Heikkonen , J , Pahikkala , T , Kotiaho , A A T , Kostiainen , R K , Varjosalo , M T & Ruskoaho , H J 2018 , ' Molecular Atlas of Postnatal Mouse Heart Development ' , Journal of the American Heart Association , vol. 7 , no. 20 , 010378 . https://doi.org/10.1161/JAHA.118.010378

Title: Molecular Atlas of Postnatal Mouse Heart Development
Author: Talman, Virpi; Teppo, Jaakko Sakari; Pöhö, Päivi Anneli; Movahedi, Parisa; Vaikkinen, Anu; Karhu, Suvi Tuuli; Trošt, Kajetan; Suvitaival, Tommi; Heikkonen, Jukka; Pahikkala, Tapio; Kotiaho, Ahti Antti Tapio; Kostiainen, Risto Kalervo; Varjosalo, Markku Tapio; Ruskoaho, Heikki Juhani
Other contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Drug Research Program
University of Helsinki, Drug Research Program
University of Helsinki, Institute of Biotechnology
University of Helsinki, Drug Research Program









Date: 2018-10-16
Language: eng
Number of pages: 46
Belongs to series: Journal of the American Heart Association
ISSN: 2047-9980
DOI: https://doi.org/10.1161/JAHA.118.010378
URI: http://hdl.handle.net/10138/256030
Abstract: Background The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of mRNA, protein, and metabolite changes in the neonatal heart for identification of metabolism‐related mechanisms associated with cardiac regeneration. Methods and Results Methods and results Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with RNA sequencing and global proteomics and metabolomics. Gene ontology analysis, KEGG pathway analysis, and fuzzy c‐means clustering were used to identify up‐ or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547 mRNAs and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS (HMG‐CoA [hydroxymethylglutaryl‐coenzyme A] synthase)–mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of HMGCS in primary neonatal cardiomyocytes reduced the percentage of BrdU‐positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle. Conclusions This study is the first systems‐level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies
Subject: heart development
heart regeneration
metabolomics
neonatalmouse cardiomyocyte
proteomics
transcriptomics
MYOCARDIAL-INFARCTION
CARDIOMYOCYTE PROLIFERATION
MEVALONATE PATHWAY
GENE-EXPRESSION
REGENERATION
METABOLISM
PROTEIN
REPAIR
YOUNG
DEDIFFERENTIATION
116 Chemical sciences
317 Pharmacy
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