Vascular Regulation by Super Enhancer-Derived LINC00607.
Vascular Regulation by Super Enhancer-Derived LINC00607.
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DOI：
10.3389/fcvm.2022.881916
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
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作者：
血管内皮细胞（ECs）在全身稳态中起着关键作用。最近的研究表明，增强子相关的长链非编码rna （lncRNAs）是EC功能的重要调节因子。我们研究了LINC00607，一种人类动脉中的超级增强子衍生的lncRNA (SE-lncRNA)，重点研究了内皮细胞。基于公共数据库和我们从健康和糖尿病供体中收集的人动脉单细胞rna测序（scRNA-seq）数据，我们发现LINC00607在动脉中大量表达，并且其水平在糖尿病人中升高。通过rna测序，我们鉴定了LINC00607在内皮细胞和血管平滑肌细胞（VSMCs）以及内皮细胞的基础和糖尿病状况中调控的转录组。此外，通过转录组学和启动子分析，我们确定c-Myc是LINC00607的上游转录因子。最后，通过scRNA-seq，我们证明了修饰的反义寡核苷酸抑制剂LINC00607可以逆转高糖和TNFα诱导的ECs功能障碍变化。总之，我们的研究展示了一种多管齐下的方法来表征血管细胞中的LINC00607及其在ECs和vsmc中的基因调控网络。我们的研究结果为se衍生的lncRNAs在血管稳态和功能障碍中的调控和功能提供了新的见解，这可能对我们理解心血管健康和糖尿病等疾病的表观遗传调控有重要影响。
Vascular endothelial cells (ECs) play a pivotal role in whole body homeostasis. Recent advances have revealed enhancer-associated long non-coding RNAs (lncRNAs) as essential regulators in EC function. We investigated LINC00607, a super enhancer-derived lncRNA (SE-lncRNA) in human arteries with an emphasis on ECs. Based on public databases and our single cell RNA-sequencing (scRNA-seq) data from human arteries collected from healthy and diabetic donors, we found that LINC00607 is abundantly expressed in the arteries and its level is increased in diabetic humans. Using RNA-sequencing, we characterized the transcriptomes regulated by LINC00607 in ECs and vascular smooth muscle cells (VSMCs) and in basal and diabetic conditions in ECs. Furthermore, through transcriptomic and promoter analysis, we identified c-Myc as an upstream transcription factor of LINC00607. Finally, using scRNA-seq, we demonstrated that modified antisense oligonucleotide inhibitor of LINC00607 can reverse dysfunctional changes induced by high glucose and TNFα in ECs. Collectively, our study demonstrates a multi-pronged approach to characterize LINC00607 in vascular cells and its gene regulatory networks in ECs and VSMCs. Our findings provide new insights into the regulation and function of SE-derived lncRNAs in both vascular homeostasis and dysfunction in a cell-type and context-dependent manner, which could have a significant impact on our understanding of epigenetic regulation implicated in cardiovascular health and diseases like diabetes.
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影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
5.6
作者：
Iaccarino I
通讯作者：
Iaccarino I
DNA甲基化介导了1型糖尿病中HBA1C相关并发症的发展。
影响因子：
20.8
作者：
Chen Z;Miao F;Braffett BH;Lachin JM;Zhang L;Wu X;Roshandel D;Carless M;Li XA;Tompkins JD;Kaddis JS;Riggs AD;Paterson AD;DCCT/EDIC Study Group;Natarajan R
通讯作者：
Natarajan R
影响因子：
--
作者：
Hart JR;Roberts TC;Weinberg MS;Morris KV;Vogt PK
通讯作者：
Vogt PK