title: ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors.
abstract: Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential to mammalian MG, we overexpressed ASCL1 in dissociated mouse MG cultures and intact retinal explants. ASCL1-infected MG upregulated retinal progenitor-specific genes and downregulated glial genes. Furthermore, ASCL1 remodeled the chromatin at its targets from a repressive to an active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers and displayed neuron-like physiological responses. These results indicate that a single transcription factor, ASCL1, can induce a neurogenic state in mature MG.
authors: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors: Julia
authors: J
authors: Pollak
authors: Matthew S
authors: MS
authors: Wilken
authors: Yumi
authors: Y
authors: Ueki
authors: Kristen E
authors: KE
authors: Cox
authors: Jane M
authors: JM
authors: Sullivan
authors: Russell J
authors: RJ
authors: Taylor
authors: Edward M
authors: EM
authors: Levine
authors: Thomas A
authors: TA
authors: Reh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D042002:Chromatin Assembly and Disassembly; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012038:Regeneration; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D055351:Retinal Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004815:Epidermal Growth Factor; D006657:Histones; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C499317:Ascl1 protein, mouse
keywords: Glia; Müller; Neurogenesis; Regeneration; Reprogramming; Retina
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