Abstract: Isolation and Characterization of a Fibroblast Sub-Population Responsible for Cutaneous Scarring in the Ventral Dermis (Plastic Surgery The Meeting)

Saturday, September 24, 2016: 1:40 PM

Tripp Leavitt, BA, BS , Plastic Surgery, Stanford University, Stanford, CA

Michael S Hu, MD, MPH, MS , Plastic Surgery, Stanford University, Stanford, CA

Graham G Walmsley, BA , Plastic Surgery, Stanford University, Stanford, CA

Ulrike Litzenburger, PhD , Dermatology, Stanford University, Stanford, CA

Ryan Chase Ransom, BA , Plastic Surgery, Stanford University, Stanford, CA

Elizabeth R Zielins, MD , Plastic Surgery, Stanford University, Stanford, CA

Derrick C. Wan, MD , Plastic and Reconstructive Surgery, Stanford University, Stanford, CA

Howard Y Chang, MD, PhD , Dermatology, Stanford University, Stanford, CA

H Peter Lorenz, MD , Plastic Surgery, Stanford University, Stanford, CA

Michael T Longaker, MD, MBA , Plastic Surgery, Children's Surgical Research, Stanford, CA

Presentation PDF file

Purpose: Recent studies have demonstrated the functional heterogeneity of fibroblasts, particularly in terms of their activities during wound healing. Both location within the dermis¹ and embryonic lineages² provide a means by which we may now identify the sub-populations of fibroblasts chiefly responsible for connective tissue deposition during scar formation in the dorsal dermis. However, whether these findings translate to the ventral dermis have yet to be elucidated.

Methods: Prrx1^Cre/Rosa26^mTmG mice, were used to trace two fibroblast lineages restricted to the ventral dermis. Fibroblasts of different embryonic lineages—based on Prrx1 expression—were isolated from ventral fetal and adult dermis at a series of time points, including the late-gestational transition from scarless to scar-forming wound healing. ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) was also performed in isolated pre- and post-gestational fibroblasts.

Results: Histological analysis revealed that the Prrx1-positive lineage contributed to the majority of connective tissue during scar formation. Flow cytometry demonstrated a shift in fibroblast sub-populations over the course of gestation. Differential transcriptional activity shown by ATAC-seq further demonstrated the heterogeneic nature of fibroblasts within the ventral dermis.

Conclusions: As in the dorsal dermis, fibroblasts of the ventral dermis demonstrate functional heterogeneity. Further studies may allow targeting of specific sub-populations to improve wound healing.

30671 Isolation and Characterization of a Fibroblast Sub-Population Responsible for Cutaneous Scarring in the Ventral Dermis