A novel paradigm for single-cell annotation in stem cell research.

Stem cell-derived models are a powerful tool for studying biology and are increasingly paving the way for cell-based therapies. However, understanding precisely which cell types are present and how closely they recapitulate in vivo cells remains challenging. Single-cell genomics, coupled with annotation methods, provides a framework for evaluating the congruence of stem cells with in vivo biology. Here, we explore approaches to cell annotation and discuss the challenges of implementing these methods in stem cell-derived models. We provide recommendations for the application of these methods, as well as our vision for the future of stem cell annotation using cell manifolds.