Abstract
In the inner ear, cochlear and vestibular sensory epithelia utilize grossly similar cell types to transduce different stimuli: sound and acceleration. Each individual sensory epithelium is composed of highly heterogeneous populations of cells based on physiological and anatomical criteria. However, limited numbers of each cell type have impeded transcriptional characterization. Here we generated transcriptomes for 301 single cells from the utricular and cochlear sensory epithelia of newborn mice to circumvent this challenge. Cluster analysis indicates distinct profiles for each of the major sensory epithelial cell types, as well as less-distinct sub-populations. Asynchrony within utricles allows reconstruction of the temporal progression of cell-type-specific differentiation and suggests possible plasticity among cells at the sensory–nonsensory boundary. Comparisons of cell types from utricles and cochleae demonstrate divergence between auditory and vestibular cells, despite a common origin. These results provide significant insights into the developmental processes that form unique inner ear cell types.
Highlights
In the inner ear, cochlear and vestibular sensory epithelia utilize grossly similar cell types to transduce different stimuli: sound and acceleration
The recent development of microfluidics-based protocols for the capture of single cells and subsequent generation of high-quality complementary DNA libraries provides a novel method for the identification of hair cells (HCs) and supporting cells (SCs) subtypes, as only a few thousand isolated cells are required for capture[22,23]
To identify HCs and SCs following isolation, LfngEGFP; R26RCAG-tdTomato; Gfi1Cre-triple transgenic mice were generated by crossing existing lines[25,26,27]
Summary
Cochlear and vestibular sensory epithelia utilize grossly similar cell types to transduce different stimuli: sound and acceleration. The mouse inner ear contains five vestibular sensory epithelia specialized for detection of linear and rotational acceleration and a single auditory epithelium, the organ of Corti. Each of these epithelia contains two primary cell types, hair cells (HCs) and supporting cells (SCs), arranged in exquisite mosaic patterns (Fig. 1a–g). HCs differentiate into subtypes with distinct electrophysiological traits (extrastriolar and striolar type-I and type-II HCs in the utricle and inner and outer HCs in the cochlea), and SCs develop elaborate cytoskeletal structures leading to unique morphologies, which in the cochlea can be categorized into at least five subtypes: inner phalangeal cells, inner and outer pillar cells, Deiters’ cells and Hensen’s cells This intricate heterogeneity is constructed on an extremely small scale. Molecular-level differences between HCs and SCs, and we find that intra-cell-type diversity at this stage is dominated by temporal and regional differences
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