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