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Updated: Jul 11, 2025

Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells
Published on: January 2, 2016
Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells
Gurmannat Kalra1, Danielle Lenz2, Dunia Abdul-Aziz2
1Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Abstract:
We explore the changes in chromatin accessibility and transcriptional programs for cochlear hair cell differentiation from postmitotic supporting cells using organoids from postnatal cochlea. The organoids contain cells with transcriptional signatures of differentiating vestibular and cochlear hair cells. Construction of trajectories identifies Lgr5+ cells as progenitors for hair cells, and the genomic data reveal gene regulatory networks leading to hair cells. We validate these networks, demonstrating dynamic changes both in expression and predicted binding sites of transcription factors (TFs) during organoid differentiation. We identify known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and the analysis predicts the regulatory factors Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt-signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for hair cell (HC) regeneration, which is limited in the adult.
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