Arteriogenesis rather than unspecialized capillary expansion is critical for restoring effective circulation to compromised tissues in patients. Deciphering the origin and specification of arterial endothelial cells during embryonic development will shed light on the understanding of adult arteriogenesis. However, during early embryonic angiogenesis, the process of endothelial diversification and molecular events underlying arteriovenous fate settling remain largely unresolved in mammals. Here, we constructed the single-cell transcriptomic landscape of vascular endothelial cells (VECs) during the time window for the occurrence of key vasculogenic and angiogenic events in both mouse and human embryos. We uncovered two distinct arterial VEC types, the major artery VECs and arterial plexus VECs, and unexpectedly divergent arteriovenous characteristics among VECs that are located in morphologically undistinguishable vascular plexus intra-embryonically. Using computational prediction and further lineage tracing of venous-featured VECs with a newly developed Nr2f2 mouse model and a dual recombinase-mediated intersectional genetic approach, we revealed early and widespread arterialization from the capillaries with considerable venous characteristics. Altogether, our findings provide unprecedented and comprehensive details of endothelial heterogeneity and lineage relationships at early angiogenesis stages, and establish a new model regarding the arteriogenesis behaviors of early intra-embryonic vasculatures.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975889PMC
http://dx.doi.org/10.1038/s41422-022-00615-zDOI Listing

Publication Analysis

Top Keywords

endothelial cells
12
early
5
vecs
5
heterogeneity endothelial
4
cells widespread
4
widespread venous
4
venous arterialization
4
arterialization early
4
early vascular
4
vascular development
4

Similar Publications

Adequate post-ischemic reperfusion of the mouse brain requires endothelial NFAT5.

Acta Neuropathol Commun

December 2024

Institute of Physiology and Pathophysiology, Department of Cardiovascular Physiology, Heidelberg University, Heidelberg, Germany.

Severity and outcome of strokes following cerebral hypoperfusion are significantly influenced by stress responses of the blood vessels. In this context, brain endothelial cells (BEC) regulate inflammation, angiogenesis and the vascular resistance to rapidly restore perfusion. Despite the relevance of these responses for infarct volume and tissue recovery, their transcriptional control in BEC is not well characterized.

View Article and Find Full Text PDF

Inflammation is a major mechanism of photoreceptor cell death in the retina during macular degeneration leading to the blindness. In this study, we investigated the role of the kinase molecule Zap70, which is an inflammatory regulator of the systemic immune system, to elucidate the control mechanism of inflammation in the retina. We observed activated microglial cells migrated and populated the retinal layer following blue LED-induced photoreceptor degeneration and activated microglial cells in the LED-injured retina expressed Zap70, unlike the inactive microglial cells in the normal retina.

View Article and Find Full Text PDF

Oxygen-glucose-deprived peripheral blood mononuclear cells act on hypoxic lesions after ischemia-reperfusion injury.

Exp Neurol

December 2024

Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata 951-8585, Japan. Electronic address:

Background: Despite advances in reperfusion therapies, ischemic stroke remains a major cause of long-term disability due to residual hypoxic lesions persisting after macrovascular reperfusion. These residual hypoxic lesions, caused by microvascular dysfunction, represent an important therapeutic target. We previously demonstrated that oxygen-glucose-deprived peripheral blood mononuclear cells (OGD-PBMCs) migrate to ischemic brain regions and promote functional recovery after stroke.

View Article and Find Full Text PDF

Intraocular pressure (IOP) is regulated through the balance of production and drainage of aqueous humor. The main route of aqueous-humor outflow comprises the trabecular meshwork (TM) and Schlemm's canal (SC). We reported that IL-6 trans-signaling can inhibit TGF-β signaling in TM cells and may affect regulation of IOP.

View Article and Find Full Text PDF

The role of the neurovascular unit in vascular cognitive impairment: Current evidence and future perspectives.

Neurobiol Dis

December 2024

Department of Neurology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130031, Jilin, China.. Electronic address:

Vascular cognitive impairment (VCI) is a progressive cognitive impairment caused by cerebrovascular disease or vascular risk factors. It is the second most common type of cognitive impairment after Alzheimer's disease. The pathogenesis of VCI is complex, and neurovascular unit destruction is one of its important mechanisms.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!