title: Comparative transcriptomic analysis identifies genes differentially expressed in human epicardial progenitors and hiPSC-derived cardiac progenitors.
abstract: Regenerative therapies hold great potential to change the treatment paradigm for cardiac diseases. Human cardiac progenitor cells can be used for drug discovery in this area and also provide a renewable source of cardiomyocytes. However, a better understanding of their characteristics is critical for interpreting data obtained from drug screening using these cells. In the present study, we performed global transcriptional analysis of two important sources of cardiac progenitors, i.e., patient epicardium-derived cells (EPDCs) and cardiac progenitor cells (CPCs) derived from human induced pluripotent stem cells. In addition, we also compared the gene expression profiles of these cells when they were cultured under normoxic and hypoxic conditions. We identified 3,289 mRNAs that were differentially expressed between EPDCs and CPCs. Gene ontology annotation and pathway enrichment analyses further revealed possible unique functions of these two cell populations. Notably, the impact of hypoxia vs normoxia on gene expression was modest and only a few genes (e.g., AK4, ALDOC, BNIP3P1, PGK1, and SLC2A1) were upregulated in EPDCs and CPCs after the cells were exposed to low oxygen for 24 h. Finally, we also performed a focused analysis of the gene expression patterns of a predefined set of 92 paracrine factors. We identified 30 of these genes as differentially expressed, and 29 were expressed at higher levels in EPDCs compared with CPCs. Taken together, the results of the present study advance our understanding of the transcriptional programs in EPDCs and CPCs and highlights important differences and similarities between these cell populations.
authors: Systems Biology Research Center, School of Bioscience, University of Skövde, Skövde, Sweden; jane.synnergren@his.se.
authors: Jane
authors: 0000-0003-4697-0590
authors: J
authors: Synnergren
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
authors: Lauren
authors: L
authors: Drowley
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
authors: Alleyn T
authors: AT
authors: Plowright
authors: Discovery Sciences, AstraZeneca Gothenburg, Mölndal, Sweden.
authors: Gabriella
authors: G
authors: Brolén
authors: Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; and.
authors: Marie-José
authors: MJ
authors: Goumans
authors: Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; and.
authors: Adriana C
authors: AC
authors: Gittenberger-de Groot
authors: Systems Biology Research Center, School of Bioscience, University of Skövde, Skövde, Sweden.|Cardiovascular and Metabolic Disease Global Medicines Development Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
authors: Peter
authors: P
authors: Sartipy
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
authors: Qing-Dong
authors: QD
authors: Wang
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D019899:Paracrine Communication / Q000235:genetics; D010496:Pericardium / Q000166:cytology*; D060066:Protein Interaction Maps / Q000187:drug effects / Q000235:genetics
chemical_list: D015415:Biomarkers; D010100:Oxygen
keywords: cardiac progenitor cells; human pluripotent stem cells; hypoxia; transcriptome