Poster Presentation Australasian Society for Dermatology Research Annual Scientific Meeting 2024

Multi-trait analysis of mouse wound healing phenotypes using reveals novel trait interaction and are further characterised by single cell level transcriptome candidate gene identification in mouse skin. (#46)

Nicholas M Muller 1 2 , Samuel X Tan 1 2 , Patrick Huang 2 , Jack Galbraith 2 , Julien Legrand 2 3 , Betoul Baz 2 4 , Edwige Roy 2 , Grant Morahan 5 , Chenhao Zhou 2 , Kiarash Khosrotehrani 1 2
  1. Dermatology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
  2. Frazer Institute, University of Queensland, Woolloongabba, Queensland, Australia
  3. Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia
  4. National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology, Al Raed, Riyadh, Saudi Arabia
  5. Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia

Introduction:

The incidence and cost of both acute and chronic skin wounds is a significant burden. Wound healing is complex, and many pathways and mediators are poorly characterized. Here, we utilize the Collaborative Cross (CC) to characterize interaction between wound healing phenotypes and subsequently identify relevant genes involved in wound healing plus their expression patterns in normal skin.

 

Methods:

Recombinant inbred mice from 73 CC strains underwent two different wounding methods. Various wound healing phenotypes were quantified. Separately, we also examined the contact hypersensitivity phenotype of CC mice to clarify their innate propensity for inflammation. Multivariable interaction analysis and GWAS were conducted. Candidate genes were identified from the quantitative trait loci and characterized via single cell transcriptome sequencing.

 

Results:

Multivariable interaction analysis revealed correlations between mast cell number and wound closure speed, and between scar area and wound closure. GWAS identified biologically feasible candidate genes, and we have demonstrated the homeostatic epidermal niche for their expression.

 

Conclusion:

Our findings on the relationship between mast cells and wound healing speed are interesting, especially considering the correlation between wound area and scar area. Higher mast cell concentrations may relate to excessive scarring, offering an avenue for further research. The identification of epidermal populations expressing candidate genes provides a basis for further investigation into their modulation and therapeutic targeting.