M. S. Hu1, T. Leavitt1, R. Ransom1, J. Garcia1, U. Litzenburger1, G. Walmsley1, C. Marshall1, L. Barnes1, A. Moore1, E. Zielins1, C. Chan1, D. Wan1, P. Lorenz1, H. Chang1, M. Longaker1 1Stanford University,Division Of Plastic Surgery, Department Of Surgery,Palo Alto, CA, USA
Introduction:
Scarring and fibrosis are an enormous public health concern, resulting in excessive morbidity and mortality, in addition to countless lost health care dollars. Currently, there are many treatments for cutaneous scarring available, but few have proven successful, and there is an estimated $12 billion annual market in the United States for such treatments. We previously identified a sub-population of fibroblasts responsible for the bulk of connective tissue deposition in the dorsal dermis during embryonic development, cutaneous wound healing, and melanoma stroma formation. Whether these findings translate to the ventral dermis has yet to be elucidated.
Methods:
Prrx1-derived fibroblasts were traced by crossing Prrx1Cre and ROSA26mTmG mice. Prrx1-derived fibroblasts were characterized using flow cytometry, histology, and ATAC-seq analysis at various stages of embryonic development.
Results:
Lineage tracing of fibroblasts within the ventral dermis revealed a sub-population, labeled by the embryonic expression of Prrx1, acting as the key contributor to connective tissue deposition during scar formation. This lineage increased as a proportion of total fibroblasts within the ventral dermis over the course of gestation, associated with the transition from scarless to scarring repair. Differential patterns of chromosomal accessibility based on ATAC-seq data further demonstrated the heterogeneic nature of fibroblasts within the ventral dermis.
Conclusion:
Analogous to findings in the dorsal dermis, fibroblasts of the ventral dermis show functional heterogeneity. Prrx1 identifies the fibroblast sub-population with fibrogenic potential in the ventral dermis. As in the dorsal dermis, selectively ablating this fibroblast sub-population may lead to decreased cutaneous scarring and a novel therapeutic to decrease scarring and fibrosis.