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Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells.
Kalra, Gurmannat; Lenz, Danielle; Abdul-Aziz, Dunia; Hanna, Craig; Basu, Mahashweta; Herb, Brian R; Colantuoni, Carlo; Milon, Beatrice; Saxena, Madhurima; Shetty, Amol C; Hertzano, Ronna; Shivdasani, Ramesh A; Ament, Seth A; Edge, Albert S B.
Afiliação
  • Kalra G; 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.
  • Lenz D; Department of Otolaryngology, Harvard Medical School, Boston, MA, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA.
  • Abdul-Aziz D; Department of Otolaryngology, Harvard Medical School, Boston, MA, USA; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA.
  • Hanna C; Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA, USA.
  • Basu M; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Herb BR; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Colantuoni C; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Milon B; Department of Otorhinolaryngology-Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Saxena M; 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.
  • Shetty AC; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Hertzano R; National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
  • Shivdasani RA; 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.
  • Ament SA; 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,
  • Edge ASB; 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. Electronic a
Cell Rep ; 42(11): 113421, 2023 11 28.
Article em En | MEDLINE | ID: mdl-37952154
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cóclea / Fatores de Transcrição Hélice-Alça-Hélice Básicos Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cóclea / Fatores de Transcrição Hélice-Alça-Hélice Básicos Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos