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Sequential regulation of glutamatergic and subtype-specific projection neuron identities in the developing cerebral cortex

ABSTRACT: Sequential regulation of glutamatergic and subtype-specific projection neuron identities in the developing cerebral cortex

PROVIDER: PRJNA596452 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10729922_1.fastq.gz	Fastqsanger.gz
	SRR10729922_2.fastq.gz	Fastqsanger.gz
	SRR10729923_1.fastq.gz	Fastqsanger.gz
	SRR10729923_2.fastq.gz	Fastqsanger.gz
	SRR10729924_1.fastq.gz	Fastqsanger.gz

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Sequential regulation of glutamatergic and subtype-specific projection neuron identities in the developing cerebral cortex

Project description:Purpose:To asses changes in gene expression profiles of cortices from the P0 wild type littermate controls and Tle4-/- null mutant mice. Methords:Total RNA was isolated and sequenced using an illumina high-seq 2500. Raw data was analyzed using TopHat. Genes were considered significantly changed whicn perform P value <= 0.05 Results: Compared to controls, 306 genes were significantly down-regulated in the Tle4 null mutant mice, and 338 genes were significantly up-regulated in the Tle4 null mutant mice.

2019-12-18 | GSE142269 | GEO

Foxp1 regulates the development of glutamatergic synaptic input onto spiny projection neurons expressing Drd2 [snRNA-seq]

Project description:Long-range glutamatergic inputs from the cortex and thalamus provide important motor and cognitive information to the striatum where they are integrated for learning and action planning. Genetic programs and transcription factors that orchestrate the development of these inputs are relatively unknown. The transcription factor, FOXP1, is crucial for the development of spiny projection neurons (SPNs) in the striatum. We investigated the cell-specific role of Foxp1 in the formation of glutamatergic inputs – including corticostriatal inputs. Embryonic Foxp1 deletion in dopamine receptor 2-expressing SPNs (D2 Foxp1cKO) leads to reduced transmission of corticostriatal excitatory inputs and decreased synaptically driven excitability. Postnatal deletion of Foxp1 also resulted in decreased glutamatergic inputs onto D2 SPNs. Single nuclei RNA sequencing of D2 Foxp1cKO striatum identified downregulated postsynaptic genes, consistent with the synaptic phenotype. Reinstating Foxp1 postnatally rescued electrophysiological deficits and expression of a subset of genes that were altered by embryonic deletion in D2 SPNs. Postnatal Foxp1 reinstatement could also rescue behavioral phenotypes. In summary, we demonstrate that FOXP1 regulates the development of corticostriatal circuitry. Further, changes at multiple levels of brain function resulting from loss of Foxp1 are rescued with postnatal Foxp1 reinstatement, indicating a therapeutic approach for individuals with FOXP1 syndrome.

2024-02-20 | GSE243662 | GEO

Single-cell atlas of thalamic projection systems

Project description:We collected single-cell RNAseq data from neurons of five thalamocortical projection systems (motor, somatosensory, visual, auditory, and prefrontal). Cells of each projection system were retrogradely labeled from their cortical target area, microdissected, and collected individually. By combining single-cell transcriptomics with in situ RNA hybridization, we found heterogeneity not only between thalamic nuclei but also within nuclei, with graded transitions between cell identities.

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Single cell sequencing and retrograde barcode tracing reveal human DA neuron identities based on projection patterns in stem cell-derived grafts

Project description:Groundbreaking research in the last decade has definitively established human pluripotent stem cells (hPSCs) as a powerful source for the unlimited generation of dopamine (DA) neurons used in cell-based therapy in Parkinson’s disease (PD). However, DA neurons constitute a heterogeneous group of cells with different molecular identities and, consequently, different functions and innervation targets. Moreover, the inaccessibility of the human brain has so far hindered our understanding of the highly complex human DA system and, therefore, the design of DA neuron subtype-specific differentiation protocols for more effective cell replacement therapies. Currently, DA neurons – located in human ventral midbrain – can only be reliably distinguished based on their projection patterns. Here, we used hPSCs to derive and then transplant DA neurons into a rat model of PD. After one year of transplantation, we performed single nucleus RNA sequencing (snRNAseq) of ~80,000 human nuclei to transcriptionally define cell type composition and obtained a comprehensive map of DA neuron molecular identities. Exploiting the fact that transplanted DA neurons innervated and integrated within the host circuitry, we then combined snRNAseq with axonal retrograde AAV barcoding to trace the projection patterns of molecularly distinct human DA neuron subtypes in the grafts. We thus defined human DA neuron transcriptional profiles based on their target-specific outgrowth in the host brain. The resulting datasets provide an unprecedented resource both for elucidating the molecular basis of human DA neuron diversity as well as for developing more targeted cell-based therapies, with major implications for outcomes of PD patients.

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Foxp1 regulates the development of glutamatergic synaptic input onto spiny projection neurons expressing Drd2 [snRNA-seq]

Project description:Foxp1 regulates the development of glutamatergic synaptic input onto spiny projection neurons expressing Drd2 [snRNA-seq]

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