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Fibroblast Heterogeneity Defines Scarring in Mouse Dermis
Michael S. Hu, MD, MPH, MS, Tripp Leavitt, MD, Mimi R. Borrelli, MD, Derrick C. Wan, MD, Geoffrey C. Gurtner, MD, H. Peter Lorenz, MD, Michael T. Longaker, MD, MBA
University of Pittsburgh
2020-02-15
Presenter: Michael Hu
Affidavit:
This abstract represents the original work performed by the presenter.
Director Name: Vu T. Nguyen
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
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 En1Cre or Prrx1Cre and ROSA26mTmG mice 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.
