Mus musculus
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ABSTRACT:
PROVIDER: PRJNA339137 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons (ChIP-Seq)
| PRJNA339139 | ENA
Project description:Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons
| PRJNA339133 | ENA
Project description:The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors (TFs), regulatory elements (REs), and chromatin are thought to precisely regulate gene expression. In the medial ganglionic eminence (MGE), the NKX2-1 TF controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. We dissected the molecular functions of NKX2-1 by defining its chromosomal binding regions, regulation of gene expression and epigenetic state. NKX2-1 binding at distal REs led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, Nkx2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub- ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
2016-09-21 | GSE85704 | GEO
Project description:The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors (TFs), regulatory elements (REs), and chromatin are thought to precisely regulate gene expression. In the medial ganglionic eminence (MGE), the NKX2-1 TF controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. We dissected the molecular functions of NKX2-1 by defining its chromosomal binding regions, regulation of gene expression and epigenetic state. NKX2-1 binding at distal REs led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, Nkx2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub- ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
2016-09-21 | GSE85703 | GEO
Project description:Genomic Resolution of DLX-orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons
| PRJNA514349 | ENA
Project description:We used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during murine forebrain development. We found several examples of clonal divergence and convergence in both neurons and glia, and examined the processes that led to clonal divergence of GABAergic neurons. Immediately after exiting the cell-cycle, GABAergic neurons originating from the same mitotic progenitor diverged into different trajectories, suggesting that differentiation into subtypes is initiated as a lineage-dependent processes at the progenitor cell level.
2021-12-15 | GSE188528 | GEO
Project description:Transplantation of GABAergic interneurons (INs) can sustain long-standing benefits in animal models of epilepsy and other neurological disorders. In a therapeutic perspective, a renewable source of functional GABAergic INs is needed. Here, we identified five factors (Foxg1, Sox2, Ascl1, Dlx5 and Lhx6) able to convert fibroblasts directly into induced GABAergic INs (iGABA-INs), displaying the molecular signature of telencephalic INs. The selected factors recapitulate in fibroblasts the activation of transcriptional networks required for the specification of GABAergic fate during telencephalon development. iGABA-INs exhibited progressively maturing firing patterns comparable to those of cortical INs, had synaptic currents and released GABA. Importantly, upon grafting in the hippocampus, iGABA-INs survived, matured and their optogenetic stimulation triggered GABAergic transmission and inhibited the activity of connected granule cells. The five factors also converted human cells into functional GABAergic neurons. These properties define iGABA-INs as a promising tool for disease modeling and cell-based therapeutic approaches. Comparison of iGABA-INs transcriptional profile with those of starting fibroblasts and GAD67-GFP+ cortical interneurons.
2015-12-15 | E-GEOD-74065 | biostudies-arrayexpress
Project description:GABAergic interneurons are lost in conditions including epilepsy and CNS injury, but there are few culture models available to study their function. Towards the goal of obtaining renewable sources of GABAergic neurons, we used the molecular profile of a functionally-incomplete GABAergic precursor clone to screen 17 new clones isolated from GFP+ rat E14.5 cortex and ganglionic eminence (GE) that were generated by viral introduction of v-myc. The clones grow as neurospheres in medium with FGF2, and after withdrawal of FGF2 they exhibit varying patterns of differentiation. Transcriptional profiling and qPCR indicated that one clone (GE6) expresses high levels of mRNAs encoding Dlx1, 2, 5 and 6, glutamate decarboxylases, and presynaptic proteins including neuropeptide Y and somatostatin. Protein expression confirmed that GE6 is a progenitor with restricted differentiation giving rise mostly to neurons with GABAergic markers. In co-cultures with hippocampal neurons, GE6 neurons became electrically excitable and received both inhibitory and excitatory synapses. After withdrawal of FGF2 in cultures of GE6 alone, neurons matured to express BetaIII-tubulin, and staining for synaptophysin and vesicular GABA transporter (VGAT) were robust after 1-2 weeks of differentiation. GE6 neurons also became electrically excitable and displayed synaptic activity, but synaptic currents were carried by chloride and were blocked by bicuculline. The results suggest that the GE6 clone, which is ventrally derived from the GE, resembles GABAergic interneuron progenitors that migrate into the developing forebrain. This is the first report of a relatively stable fetal clone that can be differentiated into GABAergic interneurons with functional synapses. The purpose was to compare differentiation patterns of several different immortalized rat neural progenitor clones to identify early stages in differentiation. The cell clones studies were: GE6 (GABAergic neuronal precursor), GE2 (non-neuronal precursor, CTX8 (multipotential precursor), L2.2 (interneuronal precursor), and L2.3 (multipotential precursor). Five rat neural precursor cell clones were compared at three different time points following FGF2 withdrawal, which triggers differentiation. Three sister culture replicates were performed for each cell clone and time point, yielding 45 samples. One microarray failed so we have 44 microarray results in the dataset.
2011-11-09 | E-GEOD-31635 | biostudies-arrayexpress
Project description:The self-renewal and differentiation potential of human embryonic stem cells (hESCs) suggests that hESCs could be used for regenerative medicine, especially for restoring neuronal functions in brain diseases. However, the functional properties of neurons derived from hESC are largely unknown. Moreover, since hESCs were derived under diverse conditions, the possibility arises that neurons derived from different hESC lines exhibit distinct properties, but this possibility remains unexplored. To address these issues, we developed a protocol that allows step-wise generation from hESCs of ~70-80% pure human neurons that form spontaneously active synaptic networks in culture. Comparison of neurons derived from the well-characterized HSF1 and HSF6 hESC lines revealed that HSF1- but not HSF6-derived neurons exhibit forebrain properties. Accordingly, HSF1-derived neurons initially form primarily GABAergic synaptic networks, whereas HSF6-derived neurons initially form glutamatergic networks. microRNA profiling revealed significant expression differences between the two hESC lines, suggesting that microRNAs may influence their distinct differentiation properties. These observations indicate that although both HSF1 and HSF6 hESCs differentiate into functional neurons, the two hESC lines exhibit distinct differentiation potentials, suggesting that they are pre-programmed. Information on hESC line-specific differentiation biases is crucial for neural stem cell therapy and establishment of novel disease models using hESCs. Experiment Overall Design: We directly compared the transcriptome of hNPCs derived from HSF-1 and HSF-6 hESC lines under two different neural induction conditions (embryonic body formation in presence of caudalizing factors (retinoic acid and bFGF) and monolayer conversion in presence of BMP signaling inhibitor (Noggin)). Since HSF6 hESC cannot undergo efficient neural differentiation without caudalizing factors, we cannot obtain RNA samples for HSF6 (Noggin). Experiment Overall Design: In summary, consistent with our immunostaining results, HSF1 hNPCs display more forebrain properties as compared to HSF6 hNPCs, indicated by expression of multiple forebrain specific markers. Conversely, HSF6 hNPCs show regional identity towards posterior central nervous system.
2008-06-16 | E-GEOD-8347 | biostudies-arrayexpress
Project description:This is an integrative genome-wide approach to identify downstream networks controlled by Pax6 during mouse lens and forebrain development. Differential gene expression was analyzed in Pax6 mouse heterozygous and wildtype newborn mouse lenses, with subsequent comparison of this data with Pax6 forebrain expression data (Holm et al., 2007). Experiment Overall Design: Three biological replicate experiments were performed from wildtype and heterozygote mice.
2008-10-26 | E-GEOD-13244 | biostudies-arrayexpress