Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds

Autor: Ryan R. Driskell, Quan M. Phan, Gerardo G. Herrera, Gracelyn M Fine, Ben Wildman, Iwona M. Driskell, Lucia Salz
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Mouse
Scars
wound healing
Regenerative medicine
Mice
dermal papilla
0302 clinical medicine
Gene expression
Medicine
Biology (General)
Cells
Cultured
Skin
Skin repair
integumentary system
General Neuroscience
Wnt signaling pathway
General Medicine
Stem Cells and Regenerative Medicine
Cell biology
Dermal papillae
medicine.anatomical_structure
Female
Stem cell
medicine.symptom
Research Article
Cell type
Lymphoid Enhancer-Binding Factor 1
QH301-705.5
Science
Mice
Transgenic
Context (language use)
General Biochemistry
Genetics and Molecular Biology
fibroblast heterogeneity
03 medical and health sciences
Animals
Lef1
General Immunology and Microbiology
business.industry
Regeneration (biology)
Fibroblasts
Mice
Inbred C57BL
030104 developmental biology
regeneration
Ectopic expression
Wound healing
business
030217 neurology & neurosurgery
Zdroj: eLife, Vol 9 (2020)
eLife
ISSN: 2050-084X
DOI: 10.7554/elife.60066
Popis: SummaryScars are a serious health concern that impacts the clinical outcome and long-term well-being of burn victims and individuals with genetic skin conditions associated with wound healing. In this study using mouse as the model, we identify regenerative factors in neonatal skin that will transform adult skin to regenerate instead of repairing wounds with a scar, without perturbing normal development and homeostasis. We utilized single-cell RNA-sequencing (scRNA-seq) to probe unsorted cells from Regenerating, Scarring, Homeostatic, and Developing skin. Our results revealed a transient regenerative cell type in Developing skin, called papillary fibroblasts, which are defined by the expression of a canonical Wnt transcription factor Lef1. Tissue specific ablation of Lef1 inhibited skin regeneration. Importantly, ectopic expression of Lef1 in dermal fibroblasts did not disrupt development and aging, but primed adult skin to undergo enhanced regeneration. Here, we reveal the possibility of transferring the regenerative abilities of neonatal skin to adult tissue by expressing Lef1 in dermal fibroblasts. Finally, we have generated an expandable web resource with a search function to display gene expression in the context of our scRNA-seq data (https://skinregeneration.org/).
Databáze: OpenAIRE
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