Proteomics

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Proteomic analysis of mitochondrial biogenesis in cardiomyocytes differentiated from human induced pluripotent stem cell


ABSTRACT: Mitochondria play a crucial role in the differentiation and maturation of human cardiomyocytes (CMs). To identify mitochondrial pathways and regulators that are involved in cardiac differentiation and maturation, we examined human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Proteomic analysis was performed on enriched mitochondrial protein extracts isolated from hiPSC-CMs differentiated from dermal fibroblasts (dFCM) and cardiac fibroblasts (cFCM), at different days of differentiation (between 12 and 115 days), and also from adult and neonatal mouse hearts for comparison. Mitochondrial proteins with a ≥2-fold change between differentiation time points in dFCMs and cFCMs, and between adult versus neonatal mouse hearts, were subjected to Ingenuity Pathway Analysis (IPA), and some upregulated proteins were validated by immunoblotting. The highest significant upregulation was in metabolic pathways for fatty acid oxidation (FAO), the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) and branched chain amino acid (BCAA) catabolism. The top upstream regulators predicted by IPA were- peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-a), the insulin receptor and the retinoblastoma protein (Rb) transcriptional repressor. In addition, IPA and immunoblotting showed substantial upregulation of the mitochondrial LonP1 protease, which regulates mitochondrial proteostasis, energetics and metabolism. Using this proteomics approach, we have identified key metabolic and intracellular signaling pathways that are up- and down- regulated during the biogenesis of mitochondria in differentiating and maturing cardiac myocytes.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Heart, Regular Cardiac Myocyte, Stem Cell

SUBMITTER: Erdene Baljinnyam  

LAB HEAD: Junichi Sadoshima

PROVIDER: PXD014317 | Pride | 2022-05-19

REPOSITORIES: pride

Dataset's files

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Action DRS
Erdene_Day12_QE2.mzid.gz Mzid
Erdene_Day12_QE2.mzid_Erdene_Day12_QE2.MGF Mzid
Erdene_Day12_QE2.mzid_Erdene_Day12_QE2.pride.mgf.gz Mzid
Erdene_Day12_QE2.pride.mztab.gz Mztab
Erdene_Day12_QE2.raw Raw
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Publications

Proteomic analysis of mitochondrial biogenesis in cardiomyocytes differentiated from human induced pluripotent stem cells.

Venkatesh Sundararajan S   Baljinnyam Erdene E   Tong Mingming M   Kashihara Toshihide T   Yan Lin L   Liu Tong T   Li Hong H   Xie Lai-Hua LH   Nakamura Michinari M   Oka Shin-Ichi SI   Suzuki Carolyn K CK   Fraidenraich Diego D   Sadoshima Junichi J  

American journal of physiology. Regulatory, integrative and comparative physiology 20201028 4


Mitochondria play key roles in the differentiation and maturation of human cardiomyocytes (CMs). As human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold potential in the treatment of heart diseases, we sought to identify key mitochondrial pathways and regulators, which may provide targets for improving cardiac differentiation and maturation. Proteomic analysis was performed on enriched mitochondrial protein extracts isolated from hiPSC-CMs differentiated from dermal fibrob  ...[more]

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