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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIP-Seq)

ABSTRACT: The response of endothelial cells to diabetic-simulating stimuli is poorly understood. To evaluate the changes of enhancer activation status in HUVEC, genome-wide enrichment of H3K27ac (marker of enhancer and open chromatin) was examined in HUVECs treated with combined high glucose and TNF-alpha. HUVECs incubated in 25 mM mannitol were used as osmolarity control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205277 | GEO | 2023/02/08

REPOSITORIES: GEO

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (RNA-Seq I)

Project description:Vascular endothelial cells play a pivotal role in whole-body homeostasis. To test the function of human long non-coding RNA LEENE in Human umbilical vein endothelial cells (HUVEC), we inhibited LEENE by using a previously validated locked nucleic acid (LNA) GapmeR under pulsatile flow which mimics the physiological state and is characterized by elevated LEENE levels. PolyA-enriched RNA-seq was performed to examine the LEENE-regulated gene expression.

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIRP-Seq)

Project description:Chromatin-associated long non-coding RNAs (ca-lncRNAs) play important roles in transcriptional regulation. To comprehensively investigate the chromatin interactome of an enhancer-derived ca-lncRNA, LEENE, we performed the Chromatin isolation by RNA purification (ChIRP) to pull down LEENE-associated DNAs, which were subjected to DNA-seq. Specifically, we used 10 previously validated tiling nucleotides targeting different domains based on the predicted secondary structure. LEENE was overexpressed by adenovirus to enhance the ChIRP-seq signals.

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Long noncoding RNA LEENE promotes angiogenesis and ischemic recovery in diabetes models.

Project description:Impaired angiogenesis in diabetes is a key process contributing to ischemic diseases such as peripheral arterial disease. Epigenetic mechanisms, including those mediated by long noncoding RNAs (lncRNAs), are crucial links connecting diabetes and the related chronic tissue ischemia. Here we identify the lncRNA that enhances endothelial nitric oxide synthase (eNOS) expression (LEENE) as a regulator of angiogenesis and ischemic response. LEENE expression was decreased in diabetic conditions in cultured endothelial cells (ECs), mouse hind limb muscles, and human arteries. Inhibition of LEENE in human microvascular ECs reduced their angiogenic capacity with a dysregulated angiogenic gene program. Diabetic mice deficient in Leene demonstrated impaired angiogenesis and perfusion following hind limb ischemia. Importantly, overexpression of human LEENE rescued the impaired ischemic response in Leene-knockout mice at tissue functional and single-cell transcriptomic levels. Mechanistically, LEENE RNA promoted transcription of proangiogenic genes in ECs, such as KDR (encoding VEGFR2) and NOS3 (encoding eNOS), potentially by interacting with LEO1, a key component of the RNA polymerase II-associated factor complex and MYC, a crucial transcription factor for angiogenesis. Taken together, our findings demonstrate an essential role for LEENE in the regulation of angiogenesis and tissue perfusion. Functional enhancement of LEENE to restore angiogenesis for tissue repair and regeneration may represent a potential strategy to tackle ischemic vascular diseases.

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-08 | GSE205287 | GEO

Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (scRNA-Seq)

Project description:To test the function of LEENE in leene-KO mice and delineate the contribution of LEENE RNA in the ischemic response, we supplemented the leene-KO mice with human LEENE RNA and performed single cell RNA-seq. The transcriptome of the EC-enriched fractions in the ischemic muscles was profiled at the single cell level.

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (RNA-Seq II)

Project description:Vascular endothelial cells play a pivotal role in whole-body homeostasis. To test the function of LEENE in leene-KO mice and delineate the contribution of LEENE RNA in the ischemic response, we supplemented the leene-KO mice with human LEENE RNA and profiled the transcriptomic changes in the EC-enriched fractions of the ischemic muscles.

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery

Project description:Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (scRNA-Seq)

Project description:Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (scRNA-Seq)

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIRP-Seq)

Project description:Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIRP-Seq)

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Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIP-Seq)

Project description:Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIP-Seq)