14.30-14.45 Ralitsa Madsen
University of Cambridge, UK
“Dosage-dependent effects of class IA phosphatidylinositol 3-kinase (PI3K) activation in human pluripotent stem cells”
Activating mutations in PIK3CA (catalytic class IA PI3K subunit) are frequent in cancer, and in isolation cause developmental overgrowth disorders. To understand the effects of PIK3CA mutations in a developmental context, we used CRISPR to knockin the strongly activating PIK3CA variant H1047Rinto one or both PIK3CA alleles ofhuman induced pluripotent stem cells.Collectively, we describe the first human developmental models of graded, endogenous PIK3CA activation, and reveal previously unappreciated dose-dependent effects on stemness.