HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1

Publication date: 21 August 2017
Source:Developmental Cell, Volume 42, Issue 4
Author(s): Juli Liu, Yang Li, Bo Lin, Yi Sheng, Lei Yang
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. Here, we 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). Overexpression of HBL1 repressed, whereas knockdown and knockout of HBL1 increased, cardiomyocyte differentiation from hiPSCs. 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. SOX2 bound to HBL1 promoter and activated its transcription. Knockdown of SOX2 in hiPSCs led to decreased HBL1 expression and increased cardiomyocyte differentiation efficiency. Thus, HBL1 plays a modulatory role in fine-tuning human-specific cardiomyocyte development by forming a regulatory network with SOX2 and MIR1.

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Teaser

Liu et al. identify a human lncRNA HBL1, which is conserved among nonhuman primates, but not other vertebrates, in the regulation of cardiomyocyte differentiation from human pluripotent stem cells. HBL1 physically interacts with MIR1 in an AGO2 complex to silence MIR1 activity and HBL1 is transcriptionally activated by SOX2.


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