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E-GEOD-45835 - Expression profiling of Ascl1-reprogrammed P12 Müller glia compared with freshly dissociated progenitors and Müller glia

Status
Released on 6 April 2013, last updated on 22 April 2013
Organism
Mus musculus
Samples (7)
Array (1)
Protocols (7)
Description
Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia cells (MG) that activate the proneural factor Achaete-scute homolog 1 (Ascl1/Mash1) and de-differentiate into progenitors cells. In contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether Ascl1 could restore a neurogenic potential to mammalian MG, we over-expressed Ascl1 in dissociated mouse MG cultures and intact retinal explants. Ascl1-infected MG upregulate retinal progenitor-specific genes, while downregulating glial genes. Furthermore, Ascl1 remodeled the chromatin at its targets from a repressive to 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 produce a neurogenic state in mature Muller glia. Expresssion profiling was used to determine the genes that were changed after Ascl1 infection of P12 cultured Müller glia compared with those present in P0 progenitors and P7-P21 Müller glia Retinas were dissociated and FAC-sorted from Hes5-GFP mice at P0, P7, P10, P14 or P21 and submitted for profiling. WT Retinas were dissociated at P12, grown for 1 week in culture, and infected with lentiviruses expressing Ascl1 or GFP for four days. Total RNA was extracted and submitted for profiling.
Experiment type
transcription profiling by array 
Contacts
THOMAS A REH <tomreh@uw.edu>, Julia Pollak, Thomas A Reh
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-45835.idf.txt
Sample and data relationshipE-GEOD-45835.sdrf.txt
Raw data (1)E-GEOD-45835.raw.1.zip
Processed data (1)E-GEOD-45835.processed.1.zip
Array designA-AFFY-130.adf.txt
Links