Human induced pluripotent stem cell modeling of neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a common monogenic disorder caused by germline mutations in a single copy of the NF1 gene. While NF1 is inherited in an autosomal dominant fashion and is completely penetrant, patients heterogeneously exhibit a wide variety of clinical features, including neurodevelopmental delays and cognitive deficits, central and peripheral nervous system tumors, and musculoskeletal and pigmentary abnormalities. Although the genetic basis for NF1 is well established, the etiologies underlying many of the associated clinical features are not well understood. Moreover, the ability to provide accurate risk assessments is currently limited, and few preclinical models fully recapitulate their human counterparts. With the advent of human induced pluripotent stem cell (hiPSC) technology, it now becomes possible to develop humanized NF1 models to gain greater insights into the pathobiology of NF1, identify and evaluate new therapeutic agents, and discover potential risk factors. In this review, we describe the current state of NF1 hiPSC research and outline potential future directions.