Fibroblast Dynamics and NR2F2 Pathway in the Development of Mouse Radiation Induced Skin Fibrosis
Year: 2024
Type: preprint
Abstract: Radiation induced skin fibrosis (RIF) is a debilitating sequela of radiation therapy. Fat grafting represents a primary therapeutic option, but its mechanism remains unknown. We aimed to delineate the cellular contributions to RIF and their part in the evolution of this disease. Furthermore, as fat grafting represents a therapeutic option employed clinically, we explored how this strategy may impact prevalence of various cellular subpopulations and pathways involved. C57BL/6J and ActinCre/ROSA26VT2/GK3 mice underwent radiation wounding and mice were euthanized at weeks 0, 2, 4, and 8 following radiation. Fibrosis had a temporal response from week 0 to 8 with progressive increases in dermal thickness and collagen density along with changes to extracellular matrix organization and loss of vascularity. Tissue-resident cells expanded clonally in response to radiation injury. With single cell RNA sequencing, five transcriptionally distinct fibroblast subpopulations were identified, creating the first murine atlas for RIF. Dynamic alterations in subpopulation prevalence were appreciated in fat grafted mice, and downregulation of the NR2F2 pathway was associated with improvement of RIF.
Source: Research Square
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Irradiated head and neck cancer soft tissue reconstruction by fat transfer., G2383577122, Nikon A1Rsi resonant spectral confocal microscope, G7737800800, Ultra high throughput sequencer for sustaining and enhancing multi-scale genomic studies, Computer Cluster, G9000024714, Reprogramming fibroblasts embryonic origins to overcome skin fibrosis and scarring., Defining the role of mechanoresponsive adipocyte-to-fibroblast transition in wound fibrosis.
OpenAlex ID: W4391559906