Generation of ABCA3 Mutant iPSCs

All human iPSCs were maintained in feeder-free conditions, cultured on Matrigel-coated (Corning) plates in mTeSR media (StemCell Technologies), and passaged using Gentle Cell Dissociation Reagent (StemCell Technologies). Reprogramming of the BU3 human iPSC line was previously reported in Kurmann et al. (65 (link)), and editing of this line to target an ABCA3:GFP fusion cassette to the endogenous ABCA3 locus (BU3^ABCA3:GFP) was previously reported in Sun et al. (39 (link)). For derivation of ABCA3 mutant patient-specific iPSC lines, dermal fibroblasts from each individual were received from Washington University School of Medicine. Genetic evaluation found no mutations in other genes associated with surfactant production, such as SFTPC or SFTPB genes. Reprogramming of dermal fibroblasts from individuals with homozygous E690K or homozygous W308R ABAC3 mutations was performed as detailed in the Supplemental Methods.