Analysis of alternative splicing in mouse tissues with differentiation, disease and development.. Mus musculus

Two major goals for regenerative medicine are to reproducibly transform adult somatic cells into a pluripotent state and to control their differentiation into specific cell fates. These goals could be furthered by obtaining a complete picture of the RNA isoforms produced by these cells due to alternative splicing (AS) and alternative promoter selection (APS). To investigate the roles of AS and APS, reciprocal exon-exon junctions were interrogated on a genome-wide scale in differentiating mouse embryonic stem cells (ESCs), mouse myometrium throughout gestation and cardiac remodeling with disease using a prototype Affymetrix microarray. Using a custom analysis package named AltAnalyze (http://www.AltAnalyze.org), we identified a large number of putative AS and APS events, the majority of which were predicted to alter protein sequence and domain composition. Over a dozen AS and APS events were validated in mouse ESCs with differentiation to embryoid bodies. Overall design: Alternative splicing analysis of mouse tissue differentiation, disease and developmental remodeling paradigms.