Using total RNA sequencing, overexpression of HBL1 was shown to repress, whereas knockdown and knockout of HBL1 increased cardiomyocyte differentiation from hiPSCs. Their data showed HBL1 physically interacted with MIR1 in an AGO2 complex. Disruption of MIR1 binding sites in HBL1 showed an effect similar to that of HBL1 knockout and SOX2 bound to HBL1 promoter and activated its transcription. Knockdown of SOX2 in hiPSCs led to decreased HBL1 expression and increased cardiomyocyte differentiation efficiency.
From their data, researchers conclude HBL1 plays a modulatory role in fine-tuning human-specific cardiomyocyte development by forming a regulatory network with SOX2 and MIR1.