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Cardiomyocyte Lineage Specification in Adult Human Cardiac Precursor Cells Via Modulation of Enhancer-Associated Long Noncoding RNA Expression.

ABSTRACT: The mechanisms controlling differentiation in adult cardiac precursor cells (CPCs) are still largely unknown. In this study, CPCs isolated from the human heart were found to produce predominantly smooth muscle cells but could be redirected to the cardiomyocyte fate by transient activation followed by inhibition of NOTCH signaling. NOTCH inhibition repressed MIR-143/145 expression, and blocked smooth muscle differentiation. Expression of the microRNAs is under control of CARMEN, a long noncoding RNA associated with an enhancer located in the MIR-143/145 locus and target of NOTCH signaling. The CARMEN/MIR-145/143 axis represents, therefore, a promising target to favor production of cardiomyocytes in cell replacement therapies.

SUBMITTER: Plaisance I

PROVIDER: S-EPMC5916868 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Cardiomyocyte Lineage Specification in Adult Human Cardiac Precursor Cells Via Modulation of Enhancer-Associated Long Noncoding RNA Expression.

Plaisance Isabelle I Perruchoud Stéphanie S Fernandez-Tenorio Miguel M Gonzales Christine C Ounzain Samir S Ruchat Patrick P Nemir Mohamed M Niggli Ernst E Pedrazzini Thierry T

JACC. Basic to translational science 20161001 6

The mechanisms controlling differentiation in adult cardiac precursor cells (CPCs) are still largely unknown. In this study, CPCs isolated from the human heart were found to produce predominantly smooth muscle cells but could be redirected to the cardiomyocyte fate by transient activation followed by inhibition of NOTCH signaling. NOTCH inhibition repressed <i>MIR-143/145</i> expression, and blocked smooth muscle differentiation. Expression of the microRNAs is under control of <i>CARMEN</i>, a l ...[more]

PMID: 29707678

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A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification.

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| S-EPMC10262180 | biostudies-literature

RNA-binding protein SAMD4A targets FGF2 to regulate cardiomyocyte lineage specification from human embryonic stem cells.

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The long noncoding RNA RNCR2 directs mouse retinal cell specification.

Project description:BackgroundRecent work has identified that many long mRNA-like noncoding RNAs (lncRNAs) are expressed in the developing nervous system. Despite their abundance, the function of these ncRNAs has remained largely unexplored. We have investigated the highly abundant lncRNA RNCR2 in regulation of mouse retinal cell differentiation.ResultsWe find that the RNCR2 is selectively expressed in a subset of both mitotic progenitors and postmitotic retinal precursor cells. ShRNA-mediated knockdown of RNCR2 results in an increase of both amacrine cells and Müller glia, indicating a role for this lncRNA in regulating retinal cell fate specification. We further report that RNCR2 RNA, which is normally nuclear-retained, can be exported from the nucleus when fused to an IRES-GFP sequence. Overexpression of RNCR2-IRES-GFP phenocopies the effects of shRNA-mediated knockdown of RNCR2, implying that forced mislocalization of RNCR2 induces a dominant-negative phenotype. Finally, we use the IRES-GFP fusion approach to identify specific domains of RNCR2 that are required for repressing both amacrine and Müller glial differentiation.ConclusionThese data demonstrate that the lncRNA RNCR2 plays a critical role in regulating mammalian retinal cell fate specification. Furthermore, we present a novel approach for generating dominant-negative constructs of lncRNAs, which may be generally useful in the functional analysis of this class of molecules.

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| S-EPMC4645594 | biostudies-literature

Loss of Ccbe1 affects cardiac-specification and cardiomyocyte differentiation in mouse embryonic stem cells.

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