High-throughput microRNA sequencing in the developing branchial arches suggests miR-92b-3p regulation of a cardiovascular gene network.

IF 2.8 3区 生物学 Q2 GENETICS & HEREDITY
Frontiers in Genetics Pub Date : 2025-02-20 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1514925
Sian Goldsworthy, Marta Losa, Nicoletta Bobola, Sam Griffiths-Jones
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引用次数: 0

Abstract

Vertebrate branchial arches (BAs) are a developmental paradigm, undergoing coordinated differentiation and morphogenesis to form various adult derivative tissues. MicroRNAs can strengthen gene regulatory networks (GRNs) to promote developmental stability. To investigate microRNA-mediated regulation in BA development, we generated a novel microRNA-sequencing dataset from mouse BAs. We identified 550 expressed microRNAs, of which approximately 20% demonstrate significant differential expression across BA domains. The three most posterior BAs and the connecting outflow tract (PBA/OFT) express genes important for cardiovascular development. We predicted microRNA-target interactions with PBA/OFT-expressed cardiovascular genes and found target sites for miR-92b-3p to be enriched. We used a dual luciferase assay to validate miR-92b-3p interactions with two transcripts encoding the fundamental cardiac transcription factors (TFs), Gata6 and Tbx20. Furthermore, we demonstrated that miR-92b-3p mimic can downregulate endogenous GATA6 and TBX20 in human embryonic stem cells (hESCs) undergoing cardiomyocyte differentiation, confirming microRNA-target binding can occur in a cardiac cell type. miR-92b-3p has previously been shown to target transcripts encoding for two other cardiac TFs, Hand2 and Mef2D. Therefore, we hypothesise that miR-92b-3p acts to stabilise cardiovascular GRNs during PBA/OFT development, through multiple microRNA-mediated regulatory networks.

发育中的鳃弓的高通量microRNA测序表明miR-92b-3p调节心血管基因网络。
脊椎动物鳃弓(BAs)是一种发育模式,经过协调分化和形态发生形成各种成体衍生组织。microrna可以加强基因调控网络(grn),促进发育稳定。为了研究microrna介导的BA发育调控,我们从小鼠BA中生成了一个新的microrna测序数据集。我们鉴定了550个表达的microrna,其中大约20%在BA结构域之间表现出显著的差异表达。三个最后的BAs和连接的流出道(PBA/OFT)表达对心血管发育重要的基因。我们预测了microrna靶点与PBA/ oft表达的心血管基因的相互作用,并发现miR-92b-3p的靶点被富集。我们使用双荧光素酶测定来验证miR-92b-3p与编码基本心脏转录因子(TFs)的两个转录本Gata6和Tbx20的相互作用。此外,我们证明miR-92b-3p模拟物可以下调内源性GATA6和TBX20在心肌细胞分化的人胚胎干细胞(hESCs)中,证实microrna靶向结合可以发生在心脏细胞类型中。miR-92b-3p先前已被证明靶向编码另外两种心脏tf, Hand2和Mef2D的转录本。因此,我们假设miR-92b-3p通过多个microrna介导的调控网络,在PBA/OFT发育过程中稳定心血管grn。
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来源期刊
Frontiers in Genetics
Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
5.50
自引率
8.10%
发文量
3491
审稿时长
14 weeks
期刊介绍: Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.
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