Spatiotemporal cellular landscape of the human utricle sensory epithelium

Abstract

Vestibular dysfunction affects individuals of all ages and becomes increasingly common with age. Despite the essential role of the utricle in balance, its molecular states and tissue architecture in humans remain poorly defined. Here, we integrated paired single-nucleus transcriptomic and epigenomic profiling with imaging-based spatial transcriptomics to characterize the human fetal utricle and its spatiotemporal patterning. We resolved transcriptionally heterogeneous, spatially segregated populations of sensory and nonsensory epithelial cells and reconstructed sensory cell differentiation across three gestational ages, showing that these cells acquire region-specific transcriptional signatures before final subtype specification. We further uncover a progressive decline in nonsensory cell proliferation accompanied by chromatin remodelling, as well as transitional epithelial populations with distinct spatial and regulatory programs. Together, these data define the molecular and spatial dynamics of the human fetal utricle and reveal cell states and regulatory pathways that provide a foundation for studying vestibular disorders and regeneration. HIGHLIGHTSO_LISpatial identity of utricular sensory hair cells precedes full subtype specification C_LIO_LIDistinct transcriptional regulators control hair cell fate and regional patterning C_LIO_LISupporting cells remodel chromatin as their proliferative capacity declines C_LIO_LITransitional epithelial cells adopt ordered states along the utricular border C_LIO_LISensory and nonsensory cells show divergent regulatory and signalling programs C_LI