Quaking regulates lineage-specific splicing patterns between early progenitor cells and is required for cardiac cell fate specification

Cell type-specific alternative splicing (AS) regulates tissue homeostasis, with several examples of AS promoting stem cell self-renewal or differentiation. However, the lineage-specific patterns of AS required for early progenitor cells of each of the three germ layers and the specific RNA binding proteins (RBPs) essential for early cell fate are unknown. To approach this question, we performed parallel RNA-seq on human embryonic stem cells (hESCs), hESC-derived definitive endoderm (DE), cardiac mesoderm (CM), and ectoderm (ECT) cells. Analysis of AS patterns in these datasets show that, unlike ECT cells, DE and CM cells display distinct and non-overlapping patterns of lineage-specific splicing. Overall design: Four independent samples analyzed: undifferentiated H9 human embryonic stem cells (UD; hESCs), definitive endoderm (DE) derived from H9 hESCs, cardiac mesoderm (CM) derived from H9 hESCs, and ectoderm (ECT) derived from H9 hESCs; 3 replicates per sample