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Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse
Mitsunobu Toyosaki1, Koichiro Homma2, Sayuri Suzuki1
1Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Scientific Reports
|December 9, 2020
Summary
Researchers reprogrammed mouse adipocytes into dermal fibroblast-like cells using specific master regulators. This novel approach could enable early closure of deep burn wounds by generating needed cells from the retained fat layer.
Area of Science:
- Regenerative Medicine
- Cellular Reprogramming
- Burn Wound Healing
Background:
- Early wound closure is critical for healing deep burns, but extensive cases lack sufficient donor sites for skin grafting.
- Dermal fibroblasts are essential for dermis formation but are often lost in deep burns.
- Adipocytes in the underlying fat layer are typically retained even in severe burns.
Purpose of the Study:
- To investigate the potential of direct reprogramming to convert mouse adipocytes into dermal fibroblast-like cells.
- To assess the efficacy of specific master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, ZEB1) in this cellular transformation.
Main Methods:
- Transfection of mouse adipocytes with a cocktail of six master regulator genes.
- Analysis of cellular morphology changes using immunocytochemistry.
- Quantitative assessment of gene expression changes using RT-PCR.
Main Results:
- Reprogrammed adipocytes exhibited shrinkage of fat droplets and adopted a spindle-shaped morphology characteristic of dermal fibroblasts.
- Downregulation of adipocyte markers (PPAR-2, c/EBP, aP2, leptin) was confirmed via RT-PCR.
- Upregulation of an anti-fibroblast marker (ER-TR7) was observed via immunocytochemistry.
Conclusions:
- Direct reprogramming successfully converted mouse adipocytes into functional dermal fibroblast-like cells.
- These reprogrammed cells hold potential for developing new therapeutic strategies for deep burn wound closure.
- This method offers a promising alternative to traditional skin grafting for extensive burns.
