Dataset Information

TMT analysis of early proteome events in direct cardiomyocyte reprogramming

ABSTRACT: Direct reprogramming of fibroblasts into cardiomyocyte-like cells (iCM) holds great potential for heart regeneration and disease modeling and may lead to future therapeutic applications in human patients with heart disease. Currently, the application of this technology is limited by our lack of understanding of the molecular mechanisms which drive direct iCM reprogramming. Using a quantitative mass spectrometry-based proteomic approach we have identified the temporal global changes in protein abundance that occur during the initial phases of iCM reprogramming. Collectively, our results show systematic and temporally distinct alterations in the levels of specific functional classes of proteins during the initiating steps of reprogramming including extracellular matrix proteins, translation factors, and chromatin-binding proteins.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Fibroblast

SUBMITTER: Todd Greco

LAB HEAD: Ileana Cristea

PROVIDER: PXD006152 | Pride | 2018-02-19

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20150501_MEF_TMT_Reprogram_nuclei.zip	Other
	2015_05_01_MEF_Nuclear48vs0_TMT1.raw	Raw
	2015_05_01_MEF_Nuclear48vs0_TMT10.raw	Raw
	2015_05_01_MEF_Nuclear48vs0_TMT11.raw	Raw
	2015_05_01_MEF_Nuclear48vs0_TMT12.raw	Raw

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Publications

Initiating Events in Direct Cardiomyocyte Reprogramming.

Sauls Kimberly K Greco Todd M TM Wang Li L Zou Meng M Villasmil Michelle M Qian Li L Cristea Ileana M IM Conlon Frank L FL

Cell reports 20180201 7

Direct reprogramming of fibroblasts into cardiomyocyte-like cells (iCM) holds great potential for heart regeneration and disease modeling and may lead to future therapeutic applications. Currently, application of this technology is limited by our lack of understanding of the molecular mechanisms that drive direct iCM reprogramming. Using a quantitative mass spectrometry-based proteomic approach, we identified the temporal global changes in protein abundance that occur during initial phases of iC ...[more]

PMID: 29444441

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Project description:Background: Lamins A/C (encoded by the LMNA gene) can lead to dilated cardiomyopathy (DCM). Objectives: This study sought to undertake proteomic analysis of myocardial tissue to explore the postgenomic phenotype of end-stage lamin heart disease. Methods: Consecutive patients with end-stage lamin heart disease (LMNA-group, n=7) and ischaemic DCM (ICM-group, n=7) undergoing heart transplantation were enrolled. Samples were obtained from left atrium(LA), left ventricle(LV), right atrium(RA), right ventricle(RV) and interventricular septum(IVS). Liquid chromatography combined with mass-spectrometry was used for protein quantification. We compared protein concentrations in cardiac samples between LMNA and ICM groups. Proteins were considered differentially abundant if the quantitative difference was 1.5-fold and corrected p-value <0.05 at a false discovery rate of 0.01. Gene ontology(GO) enrichment analysis explored the related biological processes. Results: 4,247 proteins were identified in LMNA and ICM samples, of which 633 were differentially abundant in LA, 39 in LV, 181 in RA, 52 in RV, and 85 in IVS. Abundance of lamin A/C was reduced but lamin B (LMNB) increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM while sarcomeric proteins such as titin and cardiac myosin heavy chain were generally reduced in RA/LA of LMNA. Protein expression profiling and GO enrichment analysis revealed sarcopenia, extracellular matrix(ECM) remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. Conclusion: Lamin heart disease is a biventricular and biatrial disease, characterized by sarcopenia, aberrant metabolism, and ECM remodeling. LMNB and transthyretin were unexpectedly abundant in the atria and ventricles respectively of patients with end-stage lamin heart disease potentially hinting to the possibility of compensatory responses.