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:Astroglial cells in the adult brain constitute a heterogeneous population endowed with region-specific properties. Recently, they have acquired greater relevance as active components of the adult neural stem cell (aNSC) niches. Astrocytes located in the vicinity of aNSC reservoirs are thought to regulate aNSC behaviour. We have compared the function of glial cells isolated from the postnatal and adult subventricular zone and hippocampus (two stem cell niches, where aNSCs self-renew and give rise to immature neurons), from the olfactory bulb (a neurogenic region where the immature neurons cease to proliferate and terminally differentiate) and from a non-stem and non-neurogenic area such as the ventral mesencephalon. Co-culture experiments demonstrate that subventricular zone glial cells secrete soluble signals that promote NSC self-renewing divisions. We used microarrays to detail the global gene expression of astroglial cells isolated from four different brain regions (olfactory bulb, ventral mesencephalon, hippocampus and subventricular zone) and identified up-regulated genes coding for secreted proteins in astrocytes from the subventricular zone. Primary astrocytes were cultured from four CD-1 mouse brain regions and cells were employed for RNA extraction and hybridization on Affymetrix microarrays. Primary tissue for the astrocyte cultures was dissected from four postnatal day 3 littermate pups. The tissue from the three pups was pooled in order to reduce individual differences of expression profiles.
Project description:Astroglial cells in the adult brain constitute a heterogeneous population endowed with region-specific properties. Recently, they have acquired greater relevance as active components of the adult neural stem cell (aNSC) niches. Astrocytes located in the vicinity of aNSC reservoirs are thought to regulate aNSC behaviour. We have compared the function of glial cells isolated from the postnatal and adult subventricular zone and hippocampus (two stem cell niches, where aNSCs self-renew and give rise to immature neurons), from the olfactory bulb (a neurogenic region where the immature neurons cease to proliferate and terminally differentiate) and from a non-stem and non-neurogenic area such as the ventral mesencephalon. Co-culture experiments demonstrate that subventricular zone glial cells secrete soluble signals that promote NSC self-renewing divisions. We used microarrays to detail the global gene expression of astroglial cells isolated from four different brain regions (olfactory bulb, ventral mesencephalon, hippocampus and subventricular zone) and identified up-regulated genes coding for secreted proteins in astrocytes from the subventricular zone.
Project description:We used microarrays to compare the global programme of gene expression in primary cultures of neurons and astrocytes. These data sets were compared to the expression profiles of other tissues, including pancreatic islets, in order to identify a specific neuroendocrine program in pancreatic islets. Neurons and astrocytes were isolated from brain cortex and cultured in vitro for 7 and 20 days respectively. RNA was extracted and hybridized on Affymetrix microarrays. Two biological samples from neurons and astrocytes were analyzed.
Project description:We examined the effect of grape seed extract (GSE), which are known to protect neurons against oxidative stress, on primary cultures of hippocampal astrocytes. GSE increased interleukin-6 (IL-6) expression. Microarrays are used to examine the effects of GSE on primary cultures of hippocampal neurons and astrocytes. Experiment Overall Design: Primary cultures of hippocampal neurons were treated with 0, 1, or 10 ug/ml of GSE for 24 hrs. Primary cultures of hippocampal astrocytes were treated with 0, 1, 10, or 100 ug/ml of GSE for 24 hrs.