Fibroblast Dynamics and NR2F2 Pathway in the Development of Mouse Radiation Induced Skin Fibrosis
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..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 06. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wan, Derrick [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-3874650/v1 |
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| 520 | |a 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. | ||
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