Exploring the Heterogeneity of Keloid Fibroblasts

Dr Andrew Stevenson1, Ms Nicole Hortin1, Dr. Philip Melton2, Professor Fiona Wood3, A/Prof Mark Fear1

1Burn Injury Research Unit, University Of Western Australia, Crawley, Australia, 2Centre for Genetic Origins of Health and Disease , Perth, Australia, 3State Burns Service, Fiona Stanley Hospital, Murdoch, Australia

Abstract:

Keloid scarring is a fibroproliferative disorder of the skin of unknown pathophysiology, characterised by fibrotic tissue that extends beyond the boundaries of the original wound. The main cell type that produces extracellular matrix (ECM) proteins during the healing process is the fibroblast, and a dysregulation of these cells during wound healing is what leads to the excessive collagen deposition in keloids. Fibroblasts have been poorly characterised until recently and were once thought to be relatively homogenous (Hu et al., 2018).

Fibroblast heterogeneity has recently been explored using single cell RNA-seq (scRNA-seq) which sequences RNA from individual cells, differentiating cells by their transcriptome. scRNA-seq has been used to identify sub-populations of cells in many tissues, including skin (Tirosh et al., 2016; Tabib et al., 2018; Philippeos et al., 2018). However, there has been little phenotypic characterisation and to date there has been no published data on keloid fibroblasts.

We have performed scRNA-seq to identify subpopulations of fibroblasts using keloid tissue isolated from elective surgery patients, with preliminary analysis identifying 5 distinct fibroblast populations, confirming that keloids are heterogeneous and suggesting that subpopulations within the keloid are driving scar progression. This work has implications for not only keloids but broader treatment of scars, demonstrating that not all scar cells are alike. Future work will involve phenotypic characterisation of cell subtypes in order to devise more precise, tailored treatment for keloid scars.

References

Hu MS, Moore AL and Longaker MT. (2018) A Fibroblast Is Not a Fibroblast Is Not a Fibroblast. Journal of Investigative Dermatology 138: 729-730.

Philippeos C, Telerman SB, Oulès B, et al. (2018) Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations. Journal of Investigative Dermatology 138: 811-825.

Tabib T, Morse C, Wang T, et al. (2018) SFRP2/DPP4 and FMO1/LSP1 Define Major Fibroblast Populations in Human Skin. Journal of Investigative Dermatology 138: 802-810.

Tirosh I, Izar B, Prakadan SM, et al. (2016) Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352: 189.


Biography:

Andrew Stevenson is a postdoc working at the Burn Injury Research Unit at the University of Western Australia. He was awarded his PhD in 2016 titled “Investigating the role of epigenetics in scar maintenance” from UWA, and has been lucky to continue on this and other research focused on the mechanisms and treatment of fibrosis at the Burn Injury Research Unit.

Andrew was born and grew up in Perth, and attended the University of Western Australia at which he studied a BSc in Biochemistry and Molecular Biology, graduating with honours in 2007. After a gap year travelling Europe, he began working at the Burn Injury Research Unit as a research assistant, where he took up the offer of a PhD in 2011. Outside of science he enjoys playing guitar, wakeboarding and playing soccer.

About ANZBA

ANZBA is a not for profit organisation and the peak body for health professionals responsible for the care of the burn injured in Australia and New Zealand. ANZBA encourages higher standards of care through education, performance monitoring and research.

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