Abstract 323: A Novel Human Specific Long Noncoding RNA PG1 Controls Human Cardiogenesis via Regulating Beta-catenin Activity

Abstract

Long noncoding RNAs (lncRNAs) can regulate gene expression, signaling pathway, cellular and tissue functions at various stages. Recently, accumulating evidences suggest that lncRNAs play important roles in cell fate specification and organ development. We found hundreds of lncRNAs, which show lineage-specific expressions in human embryonic stem (ES) cell-derived multipotential cardiovascular progenitor cells (MCPs), cardiomyocytes (CMs), smooth muscle cells (SMs) or endothelial cells (ECs), by using whole transcriptome sequencing. Among MCP-specific lncRNAs, we identified a novel human lncRNA, PG1, which controls cardiovascular differentiation from human pluripotent stem cells. We found PG1 could regulate the early segregation of nascent mesoderm cells towards cardiac verse hematopoietic fate. Knockout of PG1 in human induced pluripotent stem (iPS) cells and H1 ES cells by CRISPR/Cas9 significantly increased hematopoietic differentiation from pluripotent stem cells when compared with wild type controls. Furthermore, our data suggest PG1 could bind beta-catenin protein to modulate Wnt signaling activity to regulate nascent mesoderm specification. In summary, we identified a novel human specific lncRNA, PG1, which plays an essential role in early stage human heart development.