HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1.
Dev Cell
; 42(4): 333-348.e5, 2017 08 21.
Article
en En
| MEDLINE
| ID: mdl-28829943
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Miocitos Cardíacos
/
Factores de Transcripción SOXB1
/
Células Madre Pluripotentes Inducidas
/
ARN Largo no Codificante
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2017
Tipo del documento:
Article