The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis
Journal Title
Development
Publication Type
epub ahead of print
Abstract
Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling. Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.
Publisher
Company of BIologists
Keywords
Angiogenesis; Endothelial cell; Histone acetylation; Single-cell RNA-sequencing; Sprouting
WEHI Research Division(s)
Epigenetics And Development; Advanced Technology And Biology; Bioinformatics
PubMed ID
34550360
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-10-12 07:30:08
Last Modified: 2021-10-19 11:09:14
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