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Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.
Wang, Tian; Ling, Angela H; Billings, Sara E; Hosseini, Davood K; Vaisbuch, Yona; Kim, Grace S; Atkinson, Patrick J; Sayyid, Zahra N; Aaron, Ksenia A; Wagh, Dhananjay; Pham, Nicole; Scheibinger, Mirko; Zhou, Ruiqi; Ishiyama, Akira; Moore, Lindsay S; Maria, Peter Santa; Blevins, Nikolas H; Jackler, Robert K; Alyono, Jennifer C; Kveton, John; Navaratnam, Dhasakumar; Heller, Stefan; Lopez, Ivan A; Grillet, Nicolas; Jan, Taha A; Cheng, Alan G.
Afiliação
  • Wang T; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Ling AH; Department of Otolaryngology - Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, PR China.
  • Billings SE; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Hosseini DK; Department of Otolaryngology - Head and Neck Surgery, Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  • Vaisbuch Y; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Kim GS; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Atkinson PJ; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Sayyid ZN; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Aaron KA; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Wagh D; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Pham N; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Scheibinger M; Stanford Genomics Facility, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Zhou R; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Ishiyama A; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Moore LS; Department of Otolaryngology - Head and Neck Surgery, Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  • Maria PS; Department of Head and Neck Surgery, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Blevins NH; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Jackler RK; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Alyono JC; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Kveton J; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Navaratnam D; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Heller S; Department of Surgery, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Lopez IA; Department of Surgery, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Grillet N; Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Jan TA; Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Cheng AG; Department of Head and Neck Surgery, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Nat Commun ; 15(1): 4833, 2024 Jun 06.
Article em En | MEDLINE | ID: mdl-38844821
ABSTRACT
Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regeneração / Análise de Célula Única / Transcriptoma Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regeneração / Análise de Célula Única / Transcriptoma Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article