Cardiogenesis processes in human and animals have differential dynamics, suggesting the existence of species-specific regulators during heart development. However, it remains a challenge to discover the human-specific cardiac regulatory genes, given that most coding genes are conserved. In a recent study, scientists from the University of Pittsburgh School of Medicine report the identification of a human-specific long noncoding RNA, Heart Brake LncRNA 1 (HBL1), which regulates cardiomyocyte development from human induced pluripotent stem cells (hiPSCs).

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.

 

Reference
J. Liu, Y. Li, B. Lin, Y. Sheng, L. Yang (2017) HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1 Dev. Cell. doi: 10.1016/j.devcel.2017.07.023 [abstract]

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