Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells

Abstract Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a la...

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Main Authors: Guillermo Albericio, Susana Aguilar, Jose Luis Torán, Rosa Yañez, Juan Antonio López, Jesús Vázquez, Carmen Mora, Antonio Bernad
Format: Article
Language:English
Published: Nature Portfolio 2022-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-03956-8
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author Guillermo Albericio
Susana Aguilar
Jose Luis Torán
Rosa Yañez
Juan Antonio López
Jesús Vázquez
Carmen Mora
Antonio Bernad
author_facet Guillermo Albericio
Susana Aguilar
Jose Luis Torán
Rosa Yañez
Juan Antonio López
Jesús Vázquez
Carmen Mora
Antonio Bernad
author_sort Guillermo Albericio
collection DOAJ
description Abstract Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.
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spelling doaj.art-d9349e50e6c24c6b821e93ac91d8f4372022-12-22T04:03:57ZengNature PortfolioScientific Reports2045-23222022-01-0112111610.1038/s41598-021-03956-8Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cellsGuillermo Albericio0Susana Aguilar1Jose Luis Torán2Rosa Yañez3Juan Antonio López4Jesús Vázquez5Carmen Mora6Antonio Bernad7Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC)Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC)Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC)Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y TecnológicasLaboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC)Laboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC)Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC)Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC)Abstract Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.https://doi.org/10.1038/s41598-021-03956-8
spellingShingle Guillermo Albericio
Susana Aguilar
Jose Luis Torán
Rosa Yañez
Juan Antonio López
Jesús Vázquez
Carmen Mora
Antonio Bernad
Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
Scientific Reports
title Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
title_full Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
title_fullStr Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
title_full_unstemmed Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
title_short Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
title_sort comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells
url https://doi.org/10.1038/s41598-021-03956-8
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