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.
The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis
Current address: Gladstone Institutes, San Francisco, CA 94158 USA
These authors contributed equally.
- Award Group:
- Funder(s): State Government of Victoria
- Award Id(s): Operational Infrastructure Support
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- Award Group:
- Funder(s): National Health and Medical Research Council
- Award Id(s): IRIISS
- Funder(s):
- Award Group:
- Funder(s): National Health and Medical Research Council
- Award Id(s): 1084248
- Funder(s):
- Award Group:
- Funder(s): Department of Education, Skills and Employment, Australian Government
- Funder(s):
- Award Group:
- Funder(s): Royal Melbourne Hospital Neuroscience Foundation
- Funder(s):
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Zoe L. Grant, Peter F. Hickey, Waruni Abeysekera, Lachlan Whitehead, Sabrina M. Lewis, Robert C. A. Symons, Tracey M. Baldwin, Daniela Amann-Zalcenstein, Alexandra L. Garnham, Gordon K. Smyth, Tim Thomas, Anne K. Voss, Leigh Coultas; The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis. Development 2021; dev.199581. doi: https://doi.org/10.1242/dev.199581
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