Definition of a cell surface signature for human cardiac progenitor cells after comprehensive comparative transcriptomic and proteomic characterization.

Juan Carlos Sepúlveda, Antonio Bernad, Paula M Alves, Jesús Vázquez, Luis R-Borlado, Itziar Palacios, Francisco Fernández-Aviles, María Eugenia Fernández, Fernando Martínez, Borja Ibanez, Carlos Galán-Arriola, José Luis Abad, José Luis Torán, Francisco Miguel Cruz, Catarina Brito, Margarida Serra, Maria João Sebastião, Isabel Moscoso, Marco Trevisan-Herraz, Carlos Torroja, Susana Aguilar, Patricia Gomes-Alves, Juan Antonio López

Journal: Scientific reports 2020;9(1):4647

PMID: 30874584

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Abstract

Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the fraction of the CPC proteome associable with specific functions by comparison with human bone marrow mesenchymal stem cells (MSC), the reference population for cell therapy, and human dermal fibroblasts (HDF), as a distant reference. Label-free proteomic analysis identified 526 proteins expressed differentially in CPC. iTRAQ analysis confirmed differential expression of a substantial proportion of those proteins in CPC relative to MSC, and systems biology analysis defined a clear overrepresentation of several categories related to enhanced angiogenic potential. The CPC plasma membrane compartment comprised 1,595 proteins, including a minimal signature of 167 proteins preferentially or exclusively expressed by CPC. CDH5 (VE-cadherin), OX2G (OX-2 membrane glycoprotein; CD200), GPR4 (G protein-coupled receptor 4), CACNG7 (calcium voltage-gated channel auxiliary subunit gamma 7) and F11R (F11 receptor; junctional adhesion molecule A; JAM-A; CD321) were selected for validation. Their differential expression was confirmed both in expanded CPC batches and in early stages of isolation, particularly when compared against cardiac fibroblasts. Among them, GPR4 demonstrated the highest discrimination capacity between all cell lineages analyzed.

Address: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049, Madrid, Spain.; Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Melchor Fernández Almagro 3, 28029, Madrid, Spain.; Laboratory of Cardiovascular Proteomics, Spanish National Cardiovascular Research Center (CNIC), Melchor Fernández Almagro 3, 28029, Madrid, Spain.; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901, Oeiras, Portugal.; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal.; Bioinformatics Unit, Spanish National Cardiovascular Research Center (CNIC), Melchor Fernández Almagro 3, 28029, Madrid, Spain.; CIMUS, Avda Barcelona s/n, Santiago de Compostela, 15782A, Coruña, Spain.; Coretherapix S.L. U. Santiago Grisolia 2, 28769, Tres Cantos, Madrid, Spain.; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; Department of Cardiology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr Esquerdo, 46, 28007, Madrid, Spain.; Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049, Madrid, Spain. [email protected].; Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Melchor Fernández Almagro 3, 28029, Madrid, Spain. [email protected].

DOI: 10.1038/s41598-019-39571-x

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MeSH Terms: Adult, Antigens, CD, Biomarkers, Cadherins, Calcium Channels, Cell Adhesion Molecules, Cell Differentiation, Gene Expression Profiling, Heart, Humans, Mesenchymal Stem Cells, Multipotent Stem Cells, Myocytes, Cardiac, Proteome, Proteomics, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Transcriptome