"Stuck in the Middle with You": intermediate cell states are not always in transition

Abstract

The era of single-cell multiomics has led to the identification of lung epithelial cells with features of both alveolar type 1 (AT1) and alveolar type 2 (AT2) pneumocytes, leading many to infer that these cells are a distinct cell type in the process of transitioning between AT2 and AT1 cells. In this issue of the JCI, Wang and colleagues demonstrated that many so-called "transitional cells" do not actually contribute to functional repair. The findings warrant a reimagining of these cells as existing in a nondirectional, intermediate cell state, rather than moving through a transitory process from one cell type to another. We look forward to further exploration of diverse cell state expression profiles and a more refined examination of hallmark gene function beyond population labeling.