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Poor proliferative capacity of adult cardiomyocytes is the primary cause of heart failure after myocardial infarction (MI), thus exploring the molecules and mechanisms that promote the proliferation of adult cardiomyocytes is crucially useful for cardiac repair after MI. Here, we found that miR-130b-5p was highly expressed in mouse embryonic and neonatal hearts and able to promote cardiomyocyte proliferation both in vitro and in vivo. Mechanistic studies revealed that miR-130b-5p mainly promoted the cardiomyocyte proliferation through the MAPK-ERK signaling pathway, and the dual-specific phosphatase 6 (Dusp6), a negative regulator of the MAPK-ERK signaling, was the direct target of miR-130b-5p. Moreover, we found that overexpression of miR-130b-5p could promote the proliferation of cardiomyocytes and improve cardiac function in mice after MI. These studies thus revealed the critical role of miR-130b-5p and its targeted MAPK-ERK signaling in the cardiomyocyte proliferation of adult hearts and proved that miR-130b-5p could be a potential target for cardiac repair after MI. [ABSTRACT FROM AUTHOR]

As crucial epigenetic regulators, long noncoding RNAs (lncRNAs) play critical functions in development processes and various diseases. However, the regulatory mechanism of lncRNAs in early heart development is still limited. In this study, we identified cardiac mesoderm-related lncRNA (LncCMRR). Knockout (KO) of LncCMRR decreased the formation potential of cardiac mesoderm and cardiomyocytes during embryoid body differentiation of mouse embryonic stem (ES) cells. Mechanistic analyses showed that LncCMRR functionally interacted with the transcription suppressor PURB and inhibited its binding potential at the promoter region of Flk1, which safeguarded the transcription of Flk1 during cardiac mesoderm formation. We also carried out gene ontology term and signaling pathway enrichment analyses for the differentially expressed genes after KO of LncCMRR, and found significant correlation of LncCMRR with cardiac muscle contraction, dilated cardiomyopathy, and hypertrophic cardiomyopathy. Consistently, the expression level of Flk1 at E7.75 and the thickness of myocardium at E17.5 were significantly decreased after KO of LncCMRR, and the survival rate and heart function index of LncCMRR-KO mice were also significantly decreased as compared with the wild-type group. These findings indicated that the defects in early heart development led to functional abnormalities in adulthood heart of LncCMRR-KO mice. Conclusively, our findings elucidate the main function and regulatory mechanism of LncCMRR in cardiac mesoderm formation, and provide new insights into lncRNA-mediated regulatory network of mouse ES cell differentiation. Graphical Abstract [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are abundantly expressed in the nervous system, but their regulatory roles in neuronal differentiation are poorly understood. Using a human embryonic stem cell (hESC)‐based 2D neural differentiation approach and a 3D cerebral organoid system, we show that SOX1‐OT variant 1 (SOX1‐OT V1), a SOX1 overlapping noncoding RNA, plays essential roles in both dorsal cortical neuron differentiation and ventral GABAergic neuron differentiation by facilitating SOX1 expression. SOX1‐OT V1 physically interacts with HDAC10 through its 5' region, acts as a decoy to block HDAC10 binding to the SOX1 promoter, and thus maintains histone acetylation levels at the SOX1 promoter. SOX1 in turn activates ASCL1 expression and promotes neuronal differentiation. Taken together, we identify a SOX1‐OT V1/HDAC10‐SOX1‐ASCL1 axis, which promotes neurogenesis, highlighting a role for lncRNAs in hESC neuronal differentiation. Synopsis: SOX1‐OT V1 interacts with HDAC10 and blocks its binding to the SOX1 promoter, maintaining histone acetylation levels at the promoter to facilitate SOX1 expression. SOX1 in turn activates ASCL1 expression to promote dorsal cortical neuron and ventral GABAergic neuron differentiation. SOX1‐OT V1 promotes histone acetylation at the SOX1 promoter.SOX1‐OT V1 acts as a decoy of HDAC10 to block HDAC10 binding to the SOX1 promoterSOX1 directly activates ASCL1 to promote hESC neuronal differentiation [ABSTRACT FROM AUTHOR]

A microdeletion within human chromosome 5q14.3 has been associated with the occurrence of neurodevelopmental disorders, such as autism and intellectual disability, and MEF2C haploinsufficiency was identified as main cause. Here, we report that a brain‐enriched long non‐coding RNA, NDIME, is located near the MEF2C locus and is required for normal neural differentiation of mouse embryonic stem cells (mESCs). NDIME interacts with EZH2, the major component of polycomb repressive complex 2 (PRC2), and blocks EZH2‐mediated trimethylation of histone H3 lysine 27 (H3K27me3) at the Mef2c promoter, promoting MEF2C transcription. Moreover, the expression levels of both NDIME and MEF2C were strongly downregulated in the hippocampus of a mouse model of autism, and the adeno‐associated virus (AAV)‐mediated expression of NDIME in the hippocampus of these mice significantly increased MEF2C expression and ameliorated autism‐like behaviors. The results of this study reveal an epigenetic mechanism by which NDIME regulates MEF2C transcription and neural differentiation and suggest potential effects and therapeutic approaches of the NDIME/MEF2C axis in autism. Synopsis: The lncRNA NDIME is required for proper neural differentiation of mESCs. Viral‐mediated expression of NDIME in the hippocampus of a mouse model of autism ameliorates autism‐like behaviors. LncRNA NDIME is a critical regulator of proper neural differentiation and functions upstream of its neighbor gene Mef2c.NDIME physically interacts with EZH2 and SUZ12, components of PRC2.NDIME is associated with autism. [ABSTRACT FROM AUTHOR]

The abundant production of methyl tert-butyl ether (MTBE) and its widespread use have led to an increase in the potential for human exposure. This work described a simple, fast, sensitive, reliable and low-cost method for the simultaneous measurement of MTBE and its metabolite, tert-butyl alcohol (TBA) in human serum by headspace solid-phase microextraction gas chromatography-mass spectrometry. Extraction conditions were optimized and 40 °C, 10 min, 250 rpm and 0.3 g NaCl for a 1 mL sample were the optimal conditions. This method showed good analytical performance in terms of sensitivity with limits of detection in serum (1 mL) of 0.03 µg/L for MTBE and 0.05 µg/L for TBA, accuracy (mean recovery values) from 75.8% to 85.8%, precision (relative standard deviations) <10% and sample stability (biodegradation) <10% after 28 days. A verification experiment proved the reproducibility and stability of this method as well. Finally the method was used to detect 212 specimens, and the internal dose levels for MTBE in human serum were presented in China. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]