Project description:Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and glia. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
Project description:Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and glia. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
Project description:The Khakh laboratory used astrocyte selective AAVs expressing Rpl22-HA and hM4Di, a Gi DREADD, in the striatum. Mice recieved either 1 mg/kg CNO or vehicle to compare striatal astrocyte transcriptomes with and without Gi-GPCR signaling activation.
Project description:Gene expression profiling of striatum in R6/2 Huntington’s disease (HD) model mouse. Striatum gene set contained gene expression alterations in other neuronal populations, such as oligodendrocyte, astrocyte, microglia and interneuron.
Project description:STEP (striatal-enriched tyrosine phosphatase) is a brain-specific phosphatase named for its robust expression in striatum. Brains from homozygous and heterozygous STEP knockout mice and wild-type littermates were harvested, and striatum microdissected. RNA was extracted and hybridized to Affymetrix 230_2 microarray chips. n=4-5 per group. Wild-type littermates were compared with STEP +/- and -/-
Project description:STEP (striatal-enriched tyrosine phosphatase) is a brain-specific phosphatase named for its robust expression in striatum. Brains from homozygous and heterozygous STEP knockout mice and wild-type littermates were harvested, and striatum microdissected. RNA was extracted and hybridized to Affymetrix 230_2 microarray chips.
