Impaired LEF1 Activation Accelerates iPSC-Derived Keratinocytes Differentiation in Hutchinson-Gilford Progeria Syndrome

    May 2022 in “ International journal of molecular sciences ”
    Xiaojing Mao, Zheng-Mei Xiong, Huijing Xue, Markus Brown, Yantenew Gete, Reynold Yu, Linlin Sun, Kan Cao
    TLDR Faulty LEF1 activation causes faster skin cell differentiation in premature aging syndrome.
    The study investigates the differentiation of induced pluripotent stem cells (iPSCs) into keratinocytes in Hutchinson-Gilford Progeria Syndrome (HGPS). It finds that HGPS iPSCs differentiate more rapidly into keratinocytes due to impaired LEF1 activation, which affects the expression of early-stage epithelial markers K8 and K18. Using Adenine Base Editing (ABE) to partially correct the HGPS mutation reduced the accelerated differentiation and cell death in HGPS iPSCs-derived keratinocytes. These findings provide insights into the molecular basis of HGPS skin abnormalities and suggest potential therapeutic applications.
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