Melanocytes determine angiogenesis gene expression across human tissues.

Area of Science:

• Biomedical Science
• Genetics
• Dermatology

Background:

• Angiogenesis-dependent diseases show racial disparities, with potential links to pigmentation.
• Previous research identified fibromodulin as a pigment-dependent angiogenic factor, but other factors and mechanisms remain unknown.

Purpose of the Study:

• To investigate the role of pigmentation in regulating angiogenesis-related pathways and gene expression.
• To identify pigment-dependent angiogenic factors and their molecular mechanisms across different human tissues.

Main Methods:

• Comparative transcriptome analysis of Black and White individuals in artery, whole blood, and skin tissues.
• Identification and analysis of differentially expressed angiogenesis pathways and key genes.
• Investigation of the direct modulation of gene expression by pigmentation levels and the role of melanocortin 1 receptor (MC1R) signaling.

Main Results:

• Several angiogenesis pathways, including artery morphogenesis and response to vascular endothelial growth factor, were differentially expressed between racial groups.
• Key gene expression in these pathways was directly modulated by the degree of pigmentation.
• Melanocortin 1 receptor (MC1R) signaling was identified as the specific pigment production pathway controlling these genes.

Conclusions:

• Pigmentation significantly mediates the regulation of angiogenesis-related pathways and their driver genes across human tissues.
• Understanding pigment-mediated angiogenesis is crucial for precision medicine approaches to diseases with racial disparities.