Distinct Regulatory Programs Control the Latent Regenerative Potential of Dermal Fibroblasts During Wound Healing

September 2020 in “ Cell stem cell ”

Sepideh Abbasi, Sarthak Sinha, Elodie Labit, Nicole L. Rosin, Grace Yoon, Waleed Rahmani, Arzina Jaffer, Nilesh Sharma, Andrew Hagner, Prajay Shah, Rohit Arora, Jessica Yoon, Anowara Islam, Aya Uchida, Chih Kai Chang, Jo Anne Stratton, R. Wilder Scott, Fábio Rossi, T. Michael Underhill, Jeff Biernaskie

TLDR Dermal fibroblasts have adjustable roles in wound healing, with specific cells promoting regeneration or scar formation.

The study demonstrated that dermal fibroblasts have distinct roles in wound healing, with hair follicle mesenchymal progenitors contributing minimally to repair. Extrafollicular progenitors marked by Hic1 were the primary source of reparative fibroblasts, showing functional differences by promoting regeneration in the wound center and scar formation at the periphery. Single-cell RNA-seq and scATAC-seq analyses revealed specific transcriptional and regulatory signatures that facilitated mesenchymal competence for regeneration. Modulating RUNX1 and retinoic acid signaling or deleting Hic1 in wound-activated fibroblasts altered healing outcomes, indicating that reparative fibroblasts possess a latent but adjustable regenerative potential.

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