Diversity-in-a-dish: A practical framework for hiPSC model development

Human induced pluripotent stem cell (hiPSC) models inherit genetic and phenotypic variation from their donors that can influence differentiation, function, and disease phenotypes, with implications for model validity and generalizability. While diversity is widely discussed in biomedical research and extensively theorized in fields like genomics, comparable guidance remains limited in hiPSC research. Effectively, diversity-related decisions are often made implicitly without clear criteria for when inclusion is methodologically warranted. We address this by (1) analyzing how diversity is defined and operationalized in (pre)clinical research, (2) extending genomics frameworks to outline stem cell-specific recommendations for describing and reporting diversity, and (3) introducing a decision framework based on four criteria (experimental purpose, biological plausibility, platform readiness, and statistical power) to determine when and how diversity should be incorporated. The overall goal is to establish a shared basis for transparent and reproducible diversity-related design and reporting.