Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Mller 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.
ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors.
Specimen part
View SamplesGenetic deletion of Nfatc1 in mice results in profound osteoclast-poor osteopetrosis, a high bone mass state caused by a lack of osteoclast activity. We hypothesized that the family of NFATc1 regulated transcripts in the osteoclast would be enriched for genes associated with osteoclast function. We used microarrays profile gene expression in wild-type and NFATc1-deficient osteoclasts generated in vitro to identify NFATc1-dependent transcripts in osteoclasts.
NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism.
Specimen part
View SamplesLoss or reduction in function of tumor suppressor genes contributes to tumorigenesis. We identified a novel homozygous deletion of DACH1 in gliomas.
Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells.
Specimen part, Cell line
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