AUTHOR=Xu Juan , Deng Yiting , Li Guang 

TITLE=Keratin 19 (Krt19) is a novel marker gene for epicardial cells

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1385867

DOI=10.3389/fgene.2024.1385867

ISSN=1664-8021

ABSTRACT=<p>Epicardial cells regulate heart growth by secreting numerous growth factors and undergoing lineage specification into other cardiac lineages. However, the lack of specific marker genes for epicardial cells has hindered the understanding of this cell type in heart development. Through the analysis of a cardiac single cell mRNA sequencing dataset, we identified a novel epicardial gene named <italic>Keratin 19</italic> (<italic>Krt19</italic>). Further analysis of the expression patterns of <italic>Krt19</italic> and <italic>Wt1</italic>, a well-known epicardial gene, revealed their preferences in major cardiac cell types. Using lineage-tracing analysis, we analyzed <italic>Krt19-CreER</italic> labeled cells at multiple time windows and found that it labels epicardial cells at both embryonic and neonatal stages. Furthermore, we studied the function of epicardial cells using a diphtheria toxin A chain (DTA)-based cell ablation system. We discovered that <italic>Krt19-CreER</italic> labeled cells are essential for fetal heart development. Finally, we investigated the function of <italic>Krt19-CreER</italic> and <italic>Wt1-CreER</italic> labeled cells in neonatal mouse development. We observed that the <italic>Krt19-CreER</italic>; <italic>Rosa-DTA</italic> mice displayed a smaller size after tamoxifen treatment, suggesting the potential importance of <italic>Krt19-CreER</italic> labeled cells in neonatal mouse development. Additionally, we found that <italic>Wt1-CreER</italic>; <italic>Rosa-DTA</italic> mice died at early stages, likely due to defects in the kidney and spleen. In summary, we have identified <italic>Krt19</italic> as a new epicardial cell marker gene and further explored the function of epicardial cells using the <italic>Krt19-CreER</italic> and <italic>Wt1-CreER</italic>-mediated DTA ablation system.</p>