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Large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration.
Emmerich, Kevin; Hageter, John; Hoang, Thanh; Lyu, Pin; Sharrock, Abigail V; Ceisel, Anneliese; Thierer, James; Chunawala, Zeeshaan; Nimmagadda, Saumya; Palazzo, Isabella; Matthews, Frazer; Zhang, Liyun; White, David T; Rodriguez, Catalina; Graziano, Gianna; Marcos, Patrick; May, Adam; Mulligan, Tim; Reibman, Barak; Saxena, Meera T; Ackerley, David F; Qian, Jiang; Blackshaw, Seth; Horstick, Eric; Mumm, Jeff S.
Afiliación
  • Emmerich K; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Hageter J; McKusick-Nathans Institute and the Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Hoang T; Department of Biology, West Virginia University, Morgantown, WV 26505, USA.
  • Lyu P; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Sharrock AV; Department of Ophthalmology and Visual Sciences, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
  • Ceisel A; Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
  • Thierer J; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Chunawala Z; School of Biological Sciences, Victoria University of Wellington, Wellington, 6012, New Zealand.
  • Nimmagadda S; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Palazzo I; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Matthews F; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Zhang L; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • White DT; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Rodriguez C; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Graziano G; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Marcos P; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • May A; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Mulligan T; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Reibman B; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Saxena MT; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Ackerley DF; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Qian J; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Blackshaw S; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Horstick E; School of Biological Sciences, Victoria University of Wellington, Wellington, 6012, New Zealand.
  • Mumm JS; Wilmer Eye Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Development ; 2024 Jul 15.
Article en En | MEDLINE | ID: mdl-39007397
ABSTRACT
Many genes are known to regulate retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited cell loss, per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 101 genes identified seven knockouts that inhibited and eleven that promoted RGC regeneration. Surprisingly, 35 of 36 genes known/implicated as being required for regeneration following widespread retinal damage were not required for RGC regeneration, and seven even enhanced regeneration kinetics, including proneural factors neurog1, olig2, and ascl1a. Mechanistic analyses revealed ascl1a disruption increased the propensity of progenitor cells to produce RGCs; i.e., increased "fate bias". These data demonstrate plasticity in how Müller glia can convert to a stem-like state and context-specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.
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Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos