Lef1 Expression in Fibroblasts Maintains Developmental Potential in Adult Skin to Regenerate Wounds

    Quan M. Phan, Gracelyn M Fine, Lucia Salz, Gerardo G. Herrera, Ben Wildman, Iwona M. Driskell, Ryan R. Driskell
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    TLDR Lef1 helps adult skin cells maintain their ability to heal wounds and regenerate hair, but the study's methods and conclusions have been questioned.
    The study "Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds" from 2020 investigated gene expression differences associated with skin development and repair. The researchers found that overexpression of Lef1 enhanced hair follicle (HF) regeneration, a result that was significant for skin wound healing and HF regeneration. However, the study faced criticism for its use of Dermo1-Cre, which is not specific to fibroblasts, and for its interpretation of single-cell RNA sequencing data. The researchers identified developing papillary fibroblasts as a transient cell population defined by Lef1 expression, but this was not clear from the analysis. Additionally, the regenerated HFs appeared abnormal and cyst-like, contradicting the authors' claim that Lef1 overexpression enhances regeneration without other adverse phenotypes. The reviewers suggested a more thorough analysis of the data and a revision of the conclusions to reference stromal cells instead of fibroblasts specifically.
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