CRISPR/Cas9-mediated editing of VHL in induced pluripotent stem cells: A model for early cell fate in von Hippel-Lindau syndrome

Abstract

The von Hippel–Lindau (VHL) tumor suppressor gene is crucial for cellular homeostasis, and its loss leads to VHL syndrome. To model early effects of VHL deficiency, we used CRISPR/Cas9 to generate human iPSC lines with heterozygous or homozygous out-of-frame deletions in exon 1. Both clones showed normal morphology, genomic stability, expression of undifferentiated markers, and tri-lineage differentiation potential. These models offer a valuable system to study early lineage specification and tumor initiation linked to VHL loss.