The majority of our knowledge of human inner ear development comes from studies using animal models, owing to limited material and tools with which to study this in human embryos. However, the extent to which these models and the underlying molecular mechanisms recapitulate human inner ear development remains largely unknown. Thus, recent efforts have been made to develop in vitro 3D models that closely resemble inner ear morphogenesis in vivo. Two papers in this issue analyse in detail the composition of inner ear organoids (IEOs) and their relation to human tissue. Firstly, Marta Roccio and colleagues (Doda and Alonso Jimenezet al., 2023) generate IEOs from induced pluripotent stem cells (iPSCs), comparing these with early human embryos. Here, using immunostaining and single-cell RNA sequencing (scRNAseq), they demonstrate that their IEOs recapitulate key developmental stages of inner ear development and identify novel signatures for otic neuroblast, placode and epithelial cells. In addition, Karl Koehler’s group (Steinhart, Valk and Osorioet al., 2023) use their previously developed IEOs to establish an inner ear organoid development atlas, which reports gene expression data and differentiation trajectories for a number of inner ear cell types from both ectodermal and mesenchymal lineages. Using scRNAseq, the authors track the first 36 days of differentiation of iPSCs and identify markers for their respective cell types, including neuroectoderm, neural crest and placodal cells. Complimented by another single-cell analysis of IEOs from the Hashino lab published earlier this year (Uedaet al., 2023), these studies provide a comprehensive and useful resource for future studies of IEOs and a more detailed analysis of human inner ear development. These models also offer a new avenue for research into irreversible hearing loss, which can arise from the damage or loss of inner ear hair cells. With the ability to grow hair cells in vitro using IEOs, the potential therapeutic applications of these models are equally as exciting.
