The mature CNS contains PDGFRA+ oligodendrocyte progenitor cells (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.
Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma.
Specimen part
View SamplesThe immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders. Hypocretin (orexin) containing neurons of the lateral hypothalamus are clearly essential for the normal regulation of sleep and wake behaviors, and have been implicated in feeding, anxiety, depression and reward. However, little is known about the molecular phenotypes of these cells, or the mechanism of their specification. We have generated a Hcrt bacTRAP line for comprehensive translational profiling of these neuronsin vivo. From this profile, we have identified 188 transcripts, as enriched in these neurons, in additions to thousands more moderately enriched or nominally expressed. We validated many of these at the RNA and protein level, including the transcription factor Lhx9. Lhx9 protein is found in a subset of these neurons, and ablation of these gene results in a 30% loss of Hcrt neuron number, and a profound hypersomnolence in mice.This data suggests that Lhx9 may be important for specification of some Hcrt neurons, and the subsets of these neurons may contribute to discrete sleep phenotypes.
Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation.
Sex, Specimen part
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Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Specimen part
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