Biology subjects

Gonzalez, K. M.

Publications and source records attributed to Gonzalez, K. M..

3 recordsLinked to original sources

bioRxiv2022

De-differentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development

Collateral arteries act as natural bypasses which re-route blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called Artery Reassembly, aids complete cardiac regeneration in neonatal hearts, but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries, like in cardiomyocytes, is dictated by their ability to de-differentiate. We performed single cell RNA sequencing of coronary endothelial cells and identified differences in molecular profiles of neonatal and adult endothelial cells. Neonates show significant increase in actively cycling artery cells that expressed prominent de-differentiation markers. Using both, in silico pathway analyses and in vivo experiments, we show that cell cycle re-entry of pre-existing artery cells, subsequent collateral artery formation and cardiac function is dependent on arterial VegfR2. This sub-population of de-differentiated and proliferating artery cells is absent in non-regenerative P7 or adult hearts. Together, our data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to de-differentiate and proliferate.

developmental biology↗

bioRxiv2020

Dach1 extends artery networks and protects against cardiac injury

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.

developmental biology↗

bioRxiv2019

Pragmatic selection of larval mosquito diets for insectary rearing of Anopheles gambiae and Aedes aegypti

Larval mosquitoes are aquatic omnivorous scavengers which scrape food from submerged surfaces and collect suspended food particles with their mouth brushes. The composition of diets that have been used in insectaries varies widely though necessarily provides sufficient nutrition to allow colonies to be maintained. Issues such as cost, availability and experience influence which diet is selected. One component of larval diets, essential fatty acids, appears to be necessary for normal flight though deficiencies may not be evident in laboratory cages and are likely more important when mosquitoes are reared for release into the field in e.g. mark-release-recapture and genetic control activities. In this study, four diets were compared for rearing Anopheles gambiae and Aedes aegypti, all of which provide these essential fatty acids. Two diets were custom formulations specifically designed for mosquitoes (Damiens) and two were commercially available fish foods: Doctors Foster and Smith Koi Staple Diet and TetraMin Plus Flakes. Development rate, survival, dry weight and adult longevity of mosquitoes reared with these four diets were measured. The method of presentation of one diet, Koi pellets, was additionally fed in two forms, pellets or a slurry, to determine any effect of food presentation on survival and development rate. While various criteria might be selected to choose the best food, the readily-available Koi pellets resulted in development rates and adult longevity equal to the other diets, high survival to the adult stage and, additionally, this is available at low cost.

physiology↗