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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Nature Portfolio
2022-01-01
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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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institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-04-11T20:48:42Z |
publishDate | 2022-01-01 |
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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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