Molecular regulation of arteriovenous endothelial cell specification

Fang, Jennifer S.; Hirschi, Karen K.

doi:10.12688/f1000research.16701.1

Cited by 40 publications

(33 citation statements)

References 89 publications

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“…To form a functional blood circulatory system, primordial endothelial cells must be specified into arterial and venous fates (43). Arterial and venous blood vessels have different functions within the circulatory network, and the endothelial cells that line arteries and veins reflect those differences in gene expression, structure, and response to cytokines and growth factors (44,45).…”

Section: Arteriovenous Endothelial Cell Specificationmentioning

confidence: 99%

Single Cell Analysis in Vascular Biology

Chavkin

Hirschi

2020

Front. Cardiovasc. Med.

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The ability to quantify DNA, RNA, and protein variations at the single cell level has revolutionized our understanding of cellular heterogeneity within tissues. Via such analyses, individual cells within populations previously thought to be homogeneous can now be delineated into specific subpopulations expressing unique sets of genes, enabling specialized functions. In vascular biology, studies using single cell RNA sequencing have revealed extensive heterogeneity among endothelial and mural cells even within the same vessel, key intermediate cell types that arise during blood and lymphatic vessel development, and cell-type specific responses to disease. Thus, emerging new single cell analysis techniques are enabling vascular biologists to elucidate mechanisms of vascular development, homeostasis, and disease that were previously not possible. In this review, we will provide an overview of single cell analysis methods and highlight recent advances in vascular biology made possible through single cell RNA sequencing.

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Section: Arteriovenous Endothelial Cell Specificationmentioning

confidence: 99%

Single Cell Analysis in Vascular Biology

Chavkin

Hirschi

2020

Front. Cardiovasc. Med.

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“…One hypothesis is that Dach1 induces the expression of arterial EC fate determinants in all capillary ECs. Notch transcription factors are the most well recognized artery cell fate determinants described to date (Fang & Hirschi, 2019). In examining differentially expressed genes (DEGs; LogFC > 0.25) between Dach1 OE and control in each cluster, we found that Dach1 does not broadly change the level of Notch pathway genes, or any other validated artery marker, in capillary subpopulations even though it was overexpressed in virtually all ECs ( Fig.…”

Section: Dach1 Shifts the Endothelial Specification Trajectory Towardmentioning

confidence: 87%

Dach1 extends artery networks and protects against cardiac injury

Raftrey

Williams

Coronado

et al. 2020

Preprint

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Coronary artery disease (CAD) is the leading cause of death worldwide, but there are currently no available methods to stimulate growth or regeneration of artery networks in diseased hearts. Studying how arteries are built during embryonic development could illuminate strategies for re-building these vessels in the setting of ischemic heart disease. We previously found, using loss-of-function experiments, that the transcription factor Dach1 is required for coronary artery development in mouse embryos. Here, we report that Dach1 overexpression in endothelial cells (ECs) extended coronary arteries and improved survival and heart function in adult mice following myocardial infarction (MI). Dach1 overexpression increased the length and number of arterial end branches, in both heart and retinal vasculature, by causing additional capillary ECs to differentiate into arterial ECs and contribute to growing arteries. Single-cell RNA sequencing (scRNAseq) of ECs undergoing Dach1-induced arterial specification indicated that it potentiated normal artery differentiation, rather than functioning as a master regulator of artery cell fate. ScRNAseq also showed that normal arterial differentiation is accompanied by repression of lipid metabolism genes, which were also repressed by Dach1 prior to arterialization. Together, these results demonstrate that increasing the expression level of Dach1 is a novel pathway for driving specification of artery ECs and extending arterial vessels, which could be explored as a means of increasing artery coverage to mitigate the effects of CAD.

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“…Blood vessels arise early during embryogenesis to compensate for the increasing need of nutrients and oxygen of the growing and differentiating organs. Vasculogenesis, the de novo formation of blood vessels in embryo, is different from angiogenesis [83][84][85]. Whereas angiogenesis is the formation of blood vessels from existing ones, vasculogenesis is the process of differentiation of angioblasts as they coalescence to form the primitive vessel bed and is limited to the embryonic phase.…”

Section: The Vein Identity and The Link To Notchmentioning

confidence: 99%

“…Venous and lymph markers appear later, usually after day E9-9.5 [85]. Despite the different morphology origin, vasculogenesis and angiogenesis are regulated by similar mechanisms with major players being the Notch signaling pathway and VEGF; other pathways involved are BMP/TGF-β and Hedgehog (HH) [84,85].…”

Section: The Vein Identity and The Link To Notchmentioning

confidence: 99%

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COUP-TFII in Health and Disease

Polvani

Pepe

Milani

et al. 2019

Cells

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The nuclear receptors (NRs) belong to a vast family of evolutionary conserved proteins acting as ligand-activated transcription factors. Functionally, NRs are essential in embryogenesis and organogenesis and in adulthood they are involved in almost every physiological and pathological process. Our knowledge of NRs action has greatly improved in recent years, demonstrating that both their expression and activity are tightly regulated by a network of signaling pathways, miRNA and reciprocal interactions. The Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII, NR2F2) is a NR classified as an orphan due to the lack of a known natural ligand. Although its expression peaks during development, and then decreases considerably, in adult tissues, COUP-TFII is an important regulator of differentiation and it is variably implicated in tissues homeostasis. As such, alterations of its expression or its transcriptional activity have been studied and linked to a spectrum of diseases in organs and tissues of different origins. Indeed, an altered COUP-TFII expression and activity may cause infertility, abnormality in the vascular system and metabolic diseases like diabetes. Moreover, COUP-TFII is actively investigated in cancer research but its role in tumor progression is yet to be fully understood. In this review, we summarize the current understanding of COUP-TFII in healthy and pathological conditions, proposing an updated and critical view of the many functions of this NR.

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Molecular regulation of arteriovenous endothelial cell specification

Cited by 40 publications

References 89 publications

Single Cell Analysis in Vascular Biology

Single Cell Analysis in Vascular Biology

Dach1 extends artery networks and protects against cardiac injury

COUP-TFII in Health and Disease

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