@entity1 embryonic stem cells (hESCs) and neural progenitor (NP) cells are excellent models for recapitulating early neuronal development in vitro, and are key to establishing strategies for the treatment of @entity179 . While much effort had been undertaken to analyze transcriptional and epigenetic differences during the transition of hESC to NP, very little work has been performed to understand post-transcriptional changes during neuronal differentiation. @entity26364 ( @entity26364 ), a major form of post-transcriptional gene regulation, is important in @entity1 development and neuronal function. @entity1 ESC, hESC-derived NP, and @entity1 central nervous system stem cells were compared using Affymetrix exon arrays. We introduced an outlier detection approach, REAP (Regression-based Exon Array Protocol), to identify 1,737 internal exons that are predicted to undergo @entity26364 in NP compared to hESC. Experimental validation of REAP-predicted @entity26364 events indicated a threshold-dependent sensitivity ranging from 56% to 69%, at a specificity of 77% to 96%. REAP predictions significantly overlapped sets of alternative events identified using expressed sequence tags and evolutionarily conserved @entity26364 events. Our results also reveal that focusing on differentially expressed genes between hESC and NP will overlook 14% of potential @entity26364 genes. In addition, we found that REAP predictions are enriched in genes encoding @entity563 / @entity1889 kinase and @entity2234 activities. An example is a REAP-predicted alternative exon in the @entity27973 ( @entity563 / @entity1889 kinase 2) gene that is differentially included in hESC, but skipped in NP as well as in other differentiated tissues. Lastly, comparative sequence analysis revealed conserved intronic cis-regulatory elements such as the @entity68607 binding site GCAUG as being proximal to candidate @entity26364 exons, suggesting that @entity68607 may participate in the regulation of @entity26364 in NP and hESC. In summary, a new methodology for exon array analysis was introduced, leading to new insights into the complexity of @entity26364 in @entity1 embryonic stem cells and their transition to neural stem cells.

Alternative splicing events identified in XXXX embryonic stem cells and neural progenitors.

@entity1 :: ('9606', 'Species') :: ['mammalian', 'human', 'Human'] @entity68607 :: ('54715;23543', 'Gene') :: ['FOX1/2'] @entity27973 :: ('9748', 'Gene') :: ['SLK'] @entity2234 :: ('164045', 'Gene') :: ['helicase'] @entity179 :: ('MESH:D019636', 'Disease') :: ['degenerative disorders'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity1889 :: ('CHEBI:26986', 'Chemical') :: ['threonine'] @entity26364 :: ('MESH:D012327', 'Disease') :: ['Alternative RNA splicing', 'AS']
@entity1 :: (9606,Species) :: ['human']
