MassIVE MSV000088762

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Definition of germ cell lineage alternative splicing programs reveals a critical role for Quaking in specifying cardiac cell fate

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Description

Alternative splicing is critical for development. However, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-specific RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes likely arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Collectively, our results thus uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm. [doi:10.25345/C5MZ95] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: alternative splicing ; splicing ; stem cell differentiation ; Quaking ; QKI ; cell fate ; RNA processing, DIA

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Principal Investigators:
(in alphabetical order) 		William Russell, University of Texas Medical Branch, United States
Submitting User: Bill
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