A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells

Individuals with the genetic disorder alpha-1 antitrypsin deficiency (AATD) are at risk of developing lung and liver disease. Patient induced pluripotent stem cells (iPSCs) have been found to model features of AATD pathogenesis but only a handful of AATD patient iPSC lines have been published. To capture the significant phenotypic diversity of the patient population, we describe here the establishment and characterization of a curated repository of AATD iPSCs with associated disease-relevant clinical data. To highlight the utility of the repository, we selected a subset of iPSC lines for functional characterization. Selected lines were differentiated to generate both hepatic and lung cell lineages and analyzed by RNA sequencing. In addition, two iPSC lines were targeted using CRISPR/Cas9 editing to accomplish scarless repair. Repository iPSCs are available to investigators for studies of disease pathogenesis and therapeutic discovery. [Display omitted] •Establishment of a curated repository of 168 highly phenotyped AATD patient samples•Generation of 28 iPSC lines available for open sharing with the research community•Demonstration of their use to study pathogenesis in multiple disease-relevant lineages In this report, Wilson and colleagues provide a detailed molecular and functional characterization of an openly available repository of AATD iPSCs, linked with rich patient clinical data. They demonstrate the ability of these patient-derived iPSCs to model both lung and liver disease and are available for distribution to investigators interested in applying them to reveal disease mechanisms or discover novel therapeutics.