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Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons (CUT&Tag)

ABSTRACT: Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons (CUT&Tag)

PROVIDER: PRJNA1124996 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29441668_1.fastq.gz	Fastqsanger.gz
	SRR29441668_2.fastq.gz	Fastqsanger.gz
	SRR29441669_1.fastq.gz	Fastqsanger.gz
	SRR29441669_2.fastq.gz	Fastqsanger.gz
	SRR29441670_1.fastq.gz	Fastqsanger.gz

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Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons (CUT&Tag)

Project description:The connectivity, activity, and plasticity of the telencephalon are shaped by pallial and subpallial GABAergic neurons, two large populations that are produced in the embryonic medial, caudal and lateral ganglionic eminences in a highly complicated manner. Dysregulated development of GABAergic neurons is associated with neuropsychiatric disorders. However, knowledge about the specification of GABAergic neuron subtypes is limited. Here, using single-cell RNA sequencing combined with loss-of-function we delineated developmental trajectories and revealed transcriptional programs that specify GABAergic neuron subtypes in each GE lineage and transcription factors that direct lineage bifurcation decisions. Our study illuminates the control of production between pallial and subpallial populations and offers transcriptomic insights into the pathogenesis of GABAergic neuron-related disorders.

2025-04-03 | GSE270103 | GEO

Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons

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Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons (scRNA-Seq)

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Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons

Project description:Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons

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Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons (scRNA-Seq)

Project description:Transcriptomic insights into fate choice of pallial versus subpallial GABAergic neurons (scRNA-Seq)

| PRJNA1124995 | ENA

Single cell analysis of the postnatal dorsal V-SVZ reveals a role for Bmpr1a-signaling in silencing pallial germinal activity

Project description:The ventricular-subventricular zone (V-SVZ) is the largest neurogenic region of the postnatal forebrain, containing neural stem cells (NSCs) that emerge from both the embryonic pallium and subpallium. Despite of this dual origin, glutamatergic neurogenesis declines rapidly after birth, while gabaergic neurogenesis persists throughout life. We performed single-cell RNA-sequencing (scRNA-Seq) of the postnatal dorsal V-SVZ for unravelling the mechanisms leading to pallial lineage germinal activity silencing. We show that pallial NSCs enter a state of deep quiescence, characterized by high BMP-signaling, reduced transcriptional activity and Hopx expression, whilst in contrast, subpallial NSCs remain primed for activation. Induction of deep quiescence is paralleled by a rapid blockade of glutamatergic neurons production and differentiation. Finally, manipulation of Bmpr1a demonstrates its key role in mediating these effects. Together, our results highlight a central role of BMP-signaling in synchronizing quiescence induction and blockade of neuronal differentiation to rapidly silence pallial germinal activity after birth.

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Project description:Dravet syndrome (DS) is a devastating early onset refractory epilepsy syndrome caused by variants in the SCN1A gene. A disturbed GABAergic interneuron function is implicated in the progression to DS but the underlying developmental and pathophysiological mechanisms remain elusive, in particularly at the chromatin level. In this study, we utilized induced pluripotent stem cells (iPSCs) derived from DS cases and healthy donors to model disease-associated epigenetic abnormalities of GABAergic development. Employing the ATAC-Seq technique, we assessed chromatin accessibility at multiple time points (Day 0, Day 19, Day 35, and Day 65) of GABAergic differentiation. Additionally, we elucidated the effects of the commonly used anti-seizure drug valproic acid (VPA) on chromatin accessibility in GABAergic cells. The distinct dynamics in chromatin profile of DS iPSC predicted accelerated early GABAergic development, evident at D19, and diverged further from the pattern in control iPSC with continued differentiation, indicating a disrupted GABAergic maturation. Exposure to VPA at D65 reshaped the chromatin landscape at a variable extent in different iPSC-lines and rescued the observed dysfunctional development in some DS iPSC-GABA. This study provides the first comprehensive investigation on the chromatin landscape of GABAergic differentiation in DS-patient iPSC, offering valuable insights into the epigenetic dysregulations associated with interneuronal dysfunction in DS. Moreover, our detailed analysis of the chromatin changes induced by VPA in iPSC-GABA holds the potential to improve development of personalized and targeted anti-epileptic therapies.

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Z-DNA underlies the target choice of Aire by facilitating promoter poising [CUT&Tag]

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Rapid conversion of fibroblasts into functional forebrain GABAergic interneurons by direct genetic reprogramming

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

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