RT Journal Article SR Electronic T1 Chicken Auditory Supporting Cells Express Interferon Response Genes during Regeneration towards Nascent Sensory Hair Cells In Vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.21.461299 DO 10.1101/2021.09.21.461299 A1 Janesick, Amanda A1 Scheibinger, Mirko A1 Benkafadar, Nesrine A1 Kirti, Sakin A1 Heller, Stefan YR 2021 UL http://biorxiv.org/content/early/2021/09/24/2021.09.21.461299.abstract AB The avian hearing organ is the basilar papilla that, in sharp contrast to the mammalian cochlea, can regenerate sensory hair cells and thereby recover from complete deafness within weeks. The mechanisms that trigger, sustain, and terminate the regenerative response in vivo are largely unknown. Here, we profile the changes in gene expression in the chicken basilar papilla after aminoglycoside antibiotic-induced hair cell loss using RNA-sequencing. The most prominent changes in gene expression were linked to the upregulation of interferon response genes which occurred in supporting cells, confirmed by single-cell RNA-sequencing and in situ hybridization. We determined that the JAK/STAT signaling pathway is essential for the interferon gene response in supporting cells, set in motion by hair cell loss. Four days after ototoxic damage, we identified newly regenerated, nascent auditory hair cells that express genes linked to termination of the interferon response. These cells are incipient modified neurons that represent a population of hair cells en route towards obtaining their location-specific and fully functional cell identity. The robust, transient expression of immune-related genes in supporting cells suggests a potential functional involvement of JAK/STAT signaling and interferon in sensory hair cell regeneration.Competing Interest StatementThe authors have declared no competing interest.