Fig. 3

Significant alternative splicing changes occurring during stem cell differentiation. Center. Splicing factors and AS of genes involved in somatic cell reprogramming; gradient color represents splicing factor expression increase/decrease from ESCs or iPSCs to differentiated cells. Left. Scheme of ESCs or iPSCs-specific AS variants. Alternative exons and the encoded amino acids are indicated in red. Right. Differentiated cells-specific isoforms are also shown. Differences in functional properties of pluripotent versus differentiated isoforms are highlighted: FOXP1 mutually exclusive exons confer different DNA binding properties; MBD2 AS variants c and a are both enriched at the promoters of Oct4 and Nanog, but only MBD2a is able to recruit chromatin remodeling complexes to repress pluripotency factors transcription; PRDM14-ES, ZNF207 A/C and GRHL1-FL enhance somatic cells reprogramming, whereas their AS isoforms, lacking the alternative exon, counteract reprogramming