AMPKß1/ß2 isoform-specific gene expression profile in human induced pluripotent stem cells

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that, upon activation, phosphorylates a wide range of substrate proteins in order to restore cellular energy balance. AMPK is a heterotrimeric protein that is composed of three subunits: a, ß and ?. The a and ß subunits are encoded by two, the ? subunit by three genes that are expressed in a tissue- and species-specific manner. However, neither the mechanisms of how different trimer combinations affect AMPK downstream effects nor the functional properties of single isoforms are completely understood so far. We provide evidence that AMPKß1- and ß2-containing AMPK trimers lead to different gene expression profiles in a model of human induced pluripotent stem cells and thereby differentially affect lineage decision. The analysis of hiPSCs harboring a gene knockout for AMPK ß1 (PRKAB1-/-) and for AMPK ß2 (PRKAB2-/-) compared to WT hiPSCs revealed major differences in the gene expression profile in all the cell lines. This suggests an isoform-specific regulation of gene expression. Overall design: Analysis of WT as well as hiPSCs deficient for the AMPK subunit ß1 ot the subunit ß2 were analyzed by RNA-Seq. Two knockout clones of each genotype were analyzed, using four individual samples for each group.