A Developmental Atlas of Mouse Vestibular-Like Inner Ear Organoids

Inner ear sensory epithelia can be generated in vitro from embryonic stem cells. The resulting inner ear organoids represent a potentially inexhaustible source of otic tissues, including sensory hair cells and supporting cells, for in vitro manipulation. Here, we present a single-cell atlas of whole mouse embryonic stem cell-derived vestibular-like inner ear organoids at six developmental stages. Our analyses trace the genesis and developmental progression of otic progenitor cells to supporting cells and hair cells. By profiling all organoid cells, we also characterize the development of additional cell groups, such as otic mesenchyme. We further utilize our atlas to describe a proliferative phase where otic progenitors produce hair cells and otic neuroblasts, followed by a transition to a non-proliferative state. The resulting map of otic progression reveals specific time windows that can inform future research on cell cycle regulation and cell lineage specification in inner ear organoids.