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Embryonic Lineage Tracing Identifies Fibrogenic Potential in Ventral and Dorsal Mouse Dermis

Hu, Michael Sung-Min MD, MPH, MS; Leavitt, Tripp MD; Borrelli, Mimi R. MD; Wan, Derrick C. MD; Lorenz, H Peter MD; Chang, Howard Y MD, PhD; Longaker, Michael T. , MD, MBA, FACS

Plastic and Reconstructive Surgery – Global Open: July 2019 - Volume 7 - Issue 7S - p 1
doi: 10.1097/01.GOX.0000579780.26078.fc
Mountain West 2019 Abstract Supplement

University of Pittsburgh Medical Center, Pittsburgh, PA

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

INTRODUCTION: Recent studies have demonstrated the heterogeneous nature of fibroblasts, particularly in the context of scar formation during wound healing. Location within the dermis and differing embryonic lineages are emerging as means for differentiating fibroblast sub-populations, particularly regarding their role in connective tissue deposition during scar formation.

METHODS:En1- and Prrx1-derived fibroblasts were traced by crossing En1Creor Prrx1Creand ROSA26mTmGmice for analysis of the dorsal and ventral dermis, respectively. En1- and 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 dorsal and ventral dermis revealed sub-populations acting as key contributors to connective tissue deposition during scar formation. These lineages were distinct in the dorsal and ventral dermis and increased as a proportion of total fibroblasts over the course of gestation. This time point associated with the transition to wound healing with scar formation in late gestation. Differential patterns of chromosomal accessibility based on ATAC-seq data further demonstrated the heterogeneic nature of fibroblasts within the dorsal and ventral dermis.

CONCLUSION: Fibroblasts of the dorsal and ventral dermis show functional heterogeneity. Targeting specific sub-populations of fibroblasts provides the potential for reducing the cutaneous fibrotic response. These fibrogenic populations are distinct in the dorsal and ventral dermis. Characterization of these heterogeneic fibroblast lineages provides further opportunities to narrow the scope of therapeutic targets overlapping across multiple profibrotic populations.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons. All rights reserved.