Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

Gurmannat Kalra; Danielle Lenz; Dunia Abdul-Aziz; Craig Hanna; Mahashweta Basu; Brian R. Herb; Carlo Colantuoni; Beatrice Milon; Madhurima Saxena; Amol C. Shetty; Ronna Hertzano; Ramesh A. Shivdasani; Seth A. Ament; Albert S.B. Edge

Cell Reports (Nov 2023)

Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

Gurmannat Kalra,
Danielle Lenz,
Dunia Abdul-Aziz,
Craig Hanna,
Mahashweta Basu,
Brian R. Herb,
Carlo Colantuoni,
Beatrice Milon,
Madhurima Saxena,
Amol C. Shetty,
Ronna Hertzano,
Ramesh A. Shivdasani,
Seth A. Ament,
Albert S.B. Edge

Affiliations

Gurmannat Kalra: Institute 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
Danielle Lenz: Department of Otolaryngology, Harvard Medical School, Boston, MA, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA
Dunia Abdul-Aziz: Department of Otolaryngology, Harvard Medical School, Boston, MA, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA
Craig Hanna: Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA
Mahashweta Basu: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
Brian R. Herb: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
Carlo Colantuoni: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
Beatrice Milon: Department of Otorhinolaryngology-Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
Madhurima Saxena: Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
Amol C. Shetty: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
Ronna Hertzano: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA
Ramesh A. Shivdasani: Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA
Seth A. Ament: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Otorhinolaryngology-Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Albert S.B. Edge: Department of Otolaryngology, Harvard Medical School, Boston, MA, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 11
p. 113421

Abstract

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Summary: 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.

CP: Stem cell research

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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