Evaluating Cell Identity from Transcription Profiles

Summary Induced pluripotent stem cells (iPS) and direct lineage programming offer promising autologous and patient-specific sources of cells for personalized drug-testing and cell-based therapy. Before these engineered cells can be widely used, it is important to evaluate how well the engineered cell types resemble their intended target cell types. We have developed a method to generate CellScore, a cell identity score that can be used to evaluate the success of an engineered cell type in relation to both its initial and desired target cell type, which are used as references. Of 20 cell transitions tested, the most successful transitions were the iPS cells (CellScore > 0.9), while other transitions (e.g. induced hepatocytes or motor neurons) indicated incomplete transitions (CellScore < 0.5). In principle, the method can be applied to any engineered cell undergoing a cell transition, where transcription profiles are available for the reference cell types and the engineered cell type. Highlights A curated standard dataset of transcription profiles from normal cell types was created. CellScore evaluates the cell identity of engineered cell types, using the curated dataset. CellScore considers the initial and desired target cell type. CellScore identifies the most successfully engineered clones for further functional testing.