Long non-coding RNAs: Modulators of phenotypic transformation in vascular smooth muscle cells

Lu, Bing-Han; Liu, Hui-Bing; Guo, Shu-Xun; Zhang, Jie; Li, Dongxu; Chen, Zhigang; Lin, Fei; Zhao, Guoan

doi:10.3389/fcvm.2022.959955

Cited by 11 publications

(8 citation statements)

References 96 publications

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“…In our EBs several of the genes more strongly altered by hypoxia (Neat1, Zfas1, supplementary Fig. S5) have been described as regulatory elements of SMC phenotypes or associated processes [62][63][64]. Here, we can see a significant reduction in some contractile genes (Actb, Tpm2, Tpm3, Cald1 ), especially in the HX10d sample.…”

Section: Discussionmentioning

confidence: 56%

An exploration of vascular cell development in mouse embryoid bodies under hypoxia through single cell RNA-seq

Acosta-Iborra,

Puente-Santamaría,

Berrouayel

et al. 2024

Preprint

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Background: Differentiation of mouse stem cells (mESC) to embryonic bodies (EBs) is a widely used approach to model early stages of development. In this study, we employed single-cell transcriptomics to examine the effect of hypoxia on the differentiation of different cell populations in EBs. Results: We differentiated EBs for 8 or 10 days, with two time frames of hypoxic or normoxic exposure: a short window of 16h for the 8-day samples, and a 48h window for the 10-day samples, totaling four experimental conditions. The EBs were composed mainly of broad mesodermal progenitors, a limited number of endodermal precursors, and smaller groups of cells that were more advanced in their differentiation pathways. These developed groups included hemoendothelial progenitors, endothelium, cardiomyocytes, and monocyte and erythrocyte precursors. Both O2 and time of differentiation significantly influenced the distribution of cell types across conditions. Our findings revealed that hypoxia induces a pervasive cell cycle arrest signature across all identified cell populations within the EB. Despite the cell cycle arrest, vascular smooth muscle (vSMCs), endothelial, and cardiac cell populations exhibit expansion under hypoxic conditions, while normoxia favours an increase in the monocyte population. Differential proliferation of hemoendothelial progenitors does not appear to be the primary driver of endothelial cells expansion in hypoxia, as their distribution remained similar across treatments and depleted over time. We observed delays in the terminal differentiation pathway of vSMCs precursors in hypoxic conditions, which may contribute to their expansion and migration by switching to a synthetic phenotype. Additionally, oxygen concentration influenced the developmental path of hemangioblasts towards either an endothelial, or myeloid lineage. In the EBs, this was coupled with a shift in presomitic mesoderm differentiation towards endotome or musculoskeletal precursors, which may provide an additional source of progenitors with endothelial potential during oxygen deprivation. Conclusion: Our study provides novel insights into the cellular responses to hypoxia in the context of early embryonic development, thus unveiling potential mechanisms underlying blood vessel growth.

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Section: Discussionmentioning

confidence: 56%

An exploration of vascular cell development in mouse embryoid bodies under hypoxia through single cell RNA-seq

Acosta-Iborra,

Puente-Santamaría,

Berrouayel

et al. 2024

Preprint

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“…CCAAT enhancer binding protein beta (Cebpb), a pro-inflammatory mediator 46 , and maternally expressed gene 3 (Meg3), a long non-coding RNA (lncRNA) that negatively regulates TGF-β signaling and promotes VSMC proliferation [47][48][49][50] , were also enriched in this region. In contrast, expression of cardiac mesoderm enhancer-associated noncoding RNA (Carmn), a positive regulator of VSMC contractile function that is downregulated in vascular disease, and expression of Myh11, a marker of differentiated VSMCs, was enriched in the distal ascending aorta, a region that is only mildly affected in LDS mouse models 49,[51][52][53] .…”

Section: Resultsmentioning

confidence: 99%

Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model

Bramel,

Camejo,

Creamer

et al. 2024

Preprint

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Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-β (TGF-β) signaling. Although aneurysms develop throughout the arterial tree, the aortic root is a site of heightened risk. To identify molecular determinants of this vulnerability, we investigated the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1M318R/+ LDS mice by single cell and spatial transcriptomics. Reduced expression of components of the extracellular matrix-receptor apparatus and upregulation of stress and inflammatory pathways were observed in all LDS VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less differentiated, proinflammatory profile. A similar population was also identified among aortic VSMCs in a human scRNAseq dataset. Postnatal VSMC-specific Gata4 deletion reduced aortic root dilation in LDS mice, suggesting that this factor sensitizes the aortic root to the effects of impaired TGF-β signaling.

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“…The proliferation of VSMC lncRNAs NR4A3 and AK098656 induces the oxidative stress-induced proliferation of VSMCs. CDKN2B-AS1 antisense lncRNA susceptibility to the development of AH [ 161 ].…”

Section: Clinical Significance Of Lncrnas In Cardiovascular Diseasesmentioning

confidence: 99%

Clinical Significance of MicroRNAs, Long Non-Coding RNAs, and CircRNAs in Cardiovascular Diseases

Singh

Kim

Choi

et al. 2023

Cells

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Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.

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Long non-coding RNAs: Modulators of phenotypic transformation in vascular smooth muscle cells

Cited by 11 publications

References 96 publications

An exploration of vascular cell development in mouse embryoid bodies under hypoxia through single cell RNA-seq

An exploration of vascular cell development in mouse embryoid bodies under hypoxia through single cell RNA-seq

Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model

Clinical Significance of MicroRNAs, Long Non-Coding RNAs, and CircRNAs in Cardiovascular Diseases

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