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Updated: Oct 19, 2025
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In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
Published on: May 11, 2021
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The histone acetyltransferase HBO1 promotes efficient tip cell sprouting during angiogenesis
Zoe L Grant1,2, Peter F Hickey1,2, Waruni Abeysekera1,2
1The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
Development (Cambridge, England)
|September 22, 2021
Summary
The histone acetyltransferase HBO1 (H3K14ac) is crucial for blood vessel development. Its loss impairs sprouting angiogenesis by increasing tip cells, hindering migration and vessel formation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- Blood vessel growth and remodeling are vital processes in development and disease.
- Endothelial cells (ECs) exhibit transcriptional diversity and dynamic gene expression changes.
- Histone acetylation, particularly H3K14ac, plays a role in gene activation during development.
Purpose of the Study:
- To investigate the role of histone acetyltransferase HBO1 (KAT7) and H3K14ac in endothelial cell function and blood vessel development.
- To understand how HBO1 influences sprouting angiogenesis and pathological EC overgrowth.
Main Methods:
- Investigated the function of HBO1 and H3K14ac in developmental sprouting angiogenesis and pathological EC overgrowth in retinal endothelium.
- Utilized single-cell RNA sequencing of retinal ECs to analyze gene expression and cell populations.
- Examined the distribution of H3K14ac in the endothelial genome.
Main Results:
- Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth.
- Hbo1-deficient retinas showed an increased abundance of tip cells, leading to EC overcrowding.
- Tip cell migration was inefficient in Hbo1-deficient retinas, disrupting sprouting angiogenesis.
- H3K14ac was abundant in both intra- and intergenic regions of the endothelial genome.
Conclusions:
- HBO1, through H3K14ac, functions as a genome organizer essential for efficient tip cell behavior.
- HBO1 is critical for regulating tip cell dynamics necessary for proper sprouting angiogenesis.
- Targeting HBO1 may offer therapeutic strategies for diseases involving aberrant blood vessel formation.
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