Spatiotemporal dynamics of inner ear sensory and non-sensory cells revealed by single-cell transcriptomics
Taha A. Jan,
Yasmin Eltawil,
Angela H. Ling,
Leon Chen,
Daniel C. Ellwanger,
Stefan Heller,
Alan G. Cheng
Affiliations
Taha A. Jan
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94115, USA
Yasmin Eltawil
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA
Angela H. Ling
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94115, USA
Leon Chen
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA
Daniel C. Ellwanger
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Genome Analysis Unit, Amgen Research, Amgen Inc., South San Francisco, CA 94080, USA
Stefan Heller
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Corresponding author
Alan G. Cheng
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Corresponding author
Summary: The utricle is a vestibular sensory organ that requires mechanosensitive hair cells to detect linear acceleration. In neonatal mice, new hair cells are derived from non-sensory supporting cells, yet cell type diversity and mechanisms of cell addition remain poorly characterized. Here, we perform computational analyses on single-cell transcriptomes to categorize cell types and resolve 14 individual sensory and non-sensory subtypes. Along the periphery of the sensory epithelium, we uncover distinct groups of transitional epithelial cells, marked by Islr, Cnmd, and Enpep expression. By reconstructing de novo trajectories and gene dynamics, we show that as the utricle expands, Islr+ transitional epithelial cells exhibit a dynamic and proliferative phase to generate new supporting cells, followed by coordinated differentiation into hair cells. Taken together, our study reveals a sequential and coordinated process by which non-sensory epithelial cells contribute to growth of the postnatal mouse sensory epithelium.
