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Generation of specialized blood vessels via lymphatic transdifferentiation
A study of zebrafish identifies an innate mechanism of blood vessel formation through the transdifferentiation of lymphatic endothelial cells, and provides in vivo evidence for a link between cell ontogeny and functionality in endothelial cells.
- Rudra N. Das
- , Yaara Tevet
- & Karina Yaniv
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Article |
Arterialization requires the timely suppression of cell growth
Arterial development relies on the timely and MYC-dependent suppression of endothelial metabolism and the cell cycle in pre-arterial endothelial cells through Notch signalling.
- Wen Luo
- , Irene Garcia-Gonzalez
- & Rui Benedito
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Article |
Capillary cell-type specialization in the alveolus
Single-cell analysis of blood vessels in the alveolus, the site of chronic disease and virus-induced lung injury, reveals two intermingled endothelial cell types with specialized gas exchange and stem cell functions.
- Astrid Gillich
- , Fan Zhang
- & Ross J. Metzger
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Article |
Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis
The transient reactivation of ETV2 in adult human endothelial cells reprograms these cells to become adaptable vasculogenic endothelia that in three-dimensional matrices self-assemble into vascular networks that can transport blood and physiologically arborize organoids and decellularized tissues.
- Brisa Palikuqi
- , Duc-Huy T. Nguyen
- & Shahin Rafii
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Article |
Erythro-myeloid progenitors contribute endothelial cells to blood vessels
New blood vessel endothelial cells arise from differentiation of erythro-myeloid progenitor cells to complement the proliferation of pre-existing endothelial cells.
- Alice Plein
- , Alessandro Fantin
- & Christiana Ruhrberg
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Letter |
Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival
In mouse and human liver models, blood vessel perfusion and mechanical stretching release angiocrine signals from endothelial cells that lead to hepatocyte survival and liver growth.
- Linda Lorenz
- , Jennifer Axnick
- & Eckhard Lammert
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Article |
Role of glutamine synthetase in angiogenesis beyond glutamine synthesis
The enzyme glutamine synthetase is active in endothelial cell migration during angiogenesis, through autopalmitoylation and the regulation of RHOJ signalling.
- Guy Eelen
- , Charlotte Dubois
- & Peter Carmeliet
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Article |
Single-cell analysis of early progenitor cells that build coronary arteries
During development, new arteries can arise from pre-existing veins; the cell fate switch involved occurs gradually and before the onset of blood flow in mouse embryo hearts.
- Tianying Su
- , Geoff Stanley
- & Kristy Red-Horse
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Letter |
Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification
The zebrafish cloche gene is required for the formation of most endothelial and haematopoietic cells, however, it has been difficult to isolate; this study reveals that cloche encodes a PAS-domain-containing bHLH transcription factor, and a mammalian orthologue can partially rescue cloche mutants, indicating a possible conserved role in mammals.
- Sven Reischauer
- , Oliver A. Stone
- & Didier Y. R. Stainier
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Letter |
Age-dependent modulation of vascular niches for haematopoietic stem cells
Notch signalling in endothelial cells of the bone induces change in the capillaries and mesenchymal stem cells of the environment to support haematopoietic stem cell amplification.
- Anjali P. Kusumbe
- , Saravana K. Ramasamy
- & Ralf H. Adams
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Letter |
FOXO1 couples metabolic activity and growth state in the vascular endothelium
The transcription factor FOXO1 is identified as a crucial checkpoint of vascular growth, coupling the metabolic and proliferative activities of endothelial cells.
- Kerstin Wilhelm
- , Katharina Happel
- & Michael Potente
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Article |
Fatty acid carbon is essential for dNTP synthesis in endothelial cells
This study identifies a crucial role for fatty acid oxidation (FAO) in endothelial cells during angiogenesis, and reveals that fatty-acid-derived carbons are used for the de novo synthesis of nucleotides, and hence FAO stimulates vessel sprouting by increasing endothelial cell proliferation.
- Sandra Schoors
- , Ulrike Bruning
- & Peter Carmeliet
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Letter |
Piezo1 integration of vascular architecture with physiological force
The Piezo1 calcium-permeable channel is revealed to have a role in the vascular cellular response to shear stress; a mouse knockout reveals that this channel is also important for normal vascular development.
- Jing Li
- , Bing Hou
- & David J. Beech
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Letter |
Endothelial Notch activity promotes angiogenesis and osteogenesis in bone
Blood vessel growth in bone is revealed to require Notch signalling and involve a specialized form of angiogenesis that does not involve endothelial sprouts.
- Saravana K. Ramasamy
- , Anjali P. Kusumbe
- & Ralf H. Adams
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Article |
Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone
Bone homeostasis and repair declines with ageing and the mechanisms regulating the relationship between bone growth and blood vessel formation have remained unknown; this mouse study identifies the endothelial cells that promote the formation of new bone, a small microvessel subtype that can be identified by high CD31 and high Emcn expression.
- Anjali P. Kusumbe
- , Saravana K. Ramasamy
- & Ralf H. Adams
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Letter |
Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period
In mice, chronic stimulation by repetitive sounds, whisker deflection, motor activity or seizures during a postnatal developmental critical period, leads to permanent reductions in brain microvascular density, an effect that impairs oxygen delivery to neurons but can be prevented by blocking nitric oxide signalling.
- Christina Whiteus
- , Catarina Freitas
- & Jaime Grutzendler
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Letter |
Control of angiogenesis by AIBP-mediated cholesterol efflux
Gene-expression studies are used to elucidate the relationship between cholesterol regulation and angiogenesis: apolipoprotein A-1 binding protein (AIBP) is found to enhance cholesterol influx from endothelial cells to high-density lipoprotein, and the resulting cholesterol depletion alters membrane lipid order in the vasculature, leading to decreased vascular endothelial growth factor receptor signalling.
- Longhou Fang
- , Soo-Ho Choi
- & Yury I. Miller
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Article |
The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis
This study identifies a deubiquitinase (DUB) that specifically recognises and cleaves linear ubiquitin chains, implicating linear (de)ubiquitination in Wnt signalling and angiogenesis; mutations in gumby cause defects in angiogenesis in mice, and structural and biochemical analysis shows that gumby encodes a linear-ubiquitin-specific DUB.
- Elena Rivkin
- , Stephanie M. Almeida
- & Sabine P. Cordes
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Letter |
A direct and melanopsin-dependent fetal light response regulates mouse eye development
During retinal vascular development there is simultaneous regression of the hyaloid vasculature and formation of the retinal vasculature; here it is demonstrated that regression of developing vasculature is light dependent and acts via the photoreceptor melanopsin.
- Sujata Rao
- , Christina Chun
- & Richard A. Lang
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Research Highlights |
Low-flow blood-vessel pruning
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News & Views |
Blood vessels on a chip
To understand how blood vessels form and function, scientists require reproducible systems that mimic living tissues. An innovative approach based on microfabricated vessels provides a key step towards this goal.
- Claudio Franco
- & Holger Gerhardt
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Article |
Cardiac angiogenic imbalance leads to peripartum cardiomyopathy
Evidence from mice and humans indicates that peripartum cardiomyopathy (PPCM) is a vascular disease caused by excessive anti-angiogenic signalling in the peripartum period of pregnancy and that pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.
- Ian S. Patten
- , Sarosh Rana
- & Zoltan Arany
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News & Views |
Skin-cancer stem cells outwitted
Skin-cancer stem cells secrete a factor that organizes a blood-supply system to fuel tumour growth. But the same factor has another sinister function — it stimulates the stem cells to propagate uncontrollably. See Letter p.399
- Salvador Aznar Benitah
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Letter |
A vascular niche and a VEGF–Nrp1 loop regulate the initiation and stemness of skin tumours
- Benjamin Beck
- , Gregory Driessens
- & Cédric Blanpain
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Letter |
Regulation of angiogenesis by a non-canonical Wnt–Flt1 pathway in myeloid cells
- James A. Stefater III
- , Ian Lewkowich
- & Richard A. Lang
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Review Article |
Molecular mechanisms and clinical applications of angiogenesis
- Peter Carmeliet
- & Rakesh K. Jain
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Letter |
Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration
These authors describe a molecular pathway by which endothelial cells sustain liver regeneration after surgical resection. Activation of vascular endothelial growth factor-A receptor-2 in a defined subpopulation of liver endothelial cells leads to the upregulation of the endothelial-specific transcription factor Id1, which in turn induces Wnt2 and hepatocyte growth factor, which are secreted from the endothelial cells and trigger hepatocyte proliferation.
- Bi-Sen Ding
- , Daniel J. Nolan
- & Shahin Rafii
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Letter |
Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands
Here it is shown that the end products of lipid oxidation — ω-(2-carboxyethyl) pyrrole and other related pyrroles — are generated during inflammation and wound healing, and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in murine and human melanomas. These carboxyalkylpyrroles are recognized by Toll-like receptor 2 on endothelial cells, setting off a chain of events that leads to the growth of new blood vessels.
- Xiaoxia Z. West
- , Nikolay L. Malinin
- & Tatiana V. Byzova
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News & Views |
Bridges that guide and unite
To form new blood vessels, the endothelial tip cells of two existing vessels come together by the process of anastomosis. But how do they find each other? Macrophages seem to provide a bridge and mediate their union.
- Thomas Schmidt
- & Peter Carmeliet
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Letter |
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
The protein ephrin-B2 is known to be upregulated during angiogenesis — the growth of new blood vessels — but its precise function has been unclear. Here it is shown that signalling through ephrin-B2 controls vessel sprouting. Mechanistically, ephrin-B2 seems to function in part by regulating the internalization of vascular endothelial growth factor receptors (VEGFRs). The results indicate that blocking ephrin-B2 signalling might be an alternative to blocking VEGFR function to disrupt angiogenesis in tumours.
- Yingdi Wang
- , Masanori Nakayama
- & Ralf H. Adams
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Letter |
Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis
The protein ephrin-B2 is known to be upregulated during angiogenesis — the growth of new blood vessels — but its precise function has been unclear. Here it is shown that signalling through ephrin-B2 controls vessel sprouting. Mechanistically, ephrin-B2 seems to function in part by regulating the internalization of vascular endothelial growth factor receptors (VEGFRs). The results indicate that blocking ephrin-B2 signalling might be an alternative to blocking VEGFR function to disrupt angiogenesis in tumours.
- Suphansa Sawamiphak
- , Sascha Seidel
- & Amparo Acker-Palmer
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Letter |
MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis
During embryonic development, blood vessels remodel in response to blood flow. Here, a genetic pathway is described through which this mechanosensory stimulus is integrated with early developmental signals to remodel vessels of the aortic arch in zebrafish. It is found that the flow-induced transcription factor klf2a is required to induce the expression of an endothelial-specific microRNA, activating signalling through the growth factor Vegf.
- Stefania Nicoli
- , Clive Standley
- & Nathan D. Lawson
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Article |
Coronary arteries form by developmental reprogramming of venous cells
Prevailing models propose that coronary arteries in the developing heart are formed from progenitor cells originating in the proepicardium. It is found here, however, that these arteries arise from angiogenic sprouts of the major vein that returns circulating blood to the embryonic heart. Thus some differentiated venous cells retain developmental plasticity and respond to local signals to convert to coronary arteries, capillaries and veins.
- Kristy Red-Horse
- , Hiroo Ueno
- & Mark A. Krasnow