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Cortical RORb is required for layer 4 transcriptional identity and barrel integrity

ABSTRACT: Cortical RORb is required for layer 4 transcriptional identity and barrel integrity

PROVIDER: PRJNA574131 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10182344.fastq.gz	Fastqsanger.gz
	SRR10182345.fastq.gz	Fastqsanger.gz
	SRR10182346.fastq.gz	Fastqsanger.gz
	SRR10182347.fastq.gz	Fastqsanger.gz
	SRR10182348.fastq.gz	Fastqsanger.gz

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Cortical RORb is required for layer 4 transcriptional identity and barrel integrity

Project description:RNA-seq and ATAC-seq from layer 4 cortical neurons expressing RORb-gfp or GFP in an RORb KO.

2020-09-15 | GSE138001 | GEO

Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity

Project description:Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.

2016-01-08 | E-GEOD-69790 | biostudies-arrayexpress

Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity

2016-01-08 | GSE69790 | GEO

Complementary networks of cortical somatostatin interneurons enforce layer specific control

Project description:The neocortex is functionally organized into layers. Layer four receives the densest bottom up sensory inputs, while layers 2/3 and 5 receive top down inputs that may convey predictive information. A subset of cortical somatostatin (SST) neurons, the Martinotti cells, gate top down input by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5, but it is unknown whether an analogous inhibitory mechanism controls activity in layer 4. Using high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal complementary circuits in the mouse barrel cortex involving genetically distinct SST subtypes that specifically and reciprocally interconnect with excitatory cells in different layers: Martinotti cells connect with layers 2/3 and 5, whereas non-Martinotti cells connect with layer 4. By enforcing layer-specific inhibition, these parallel SST subnetworks could independently regulate the balance between bottom up and top down input.

2020-07-07 | GSE153824 | GEO

Aberrant cortical layer development of brain organoids developed from Noonan syndrome-iPSCs

Project description:Noonan syndrome (NS) is a genetic disorder mainly caused by gain-of-function mutations of SHP2. Although diverse neurological manifestations are commonly diagnosed in NS patients, mechanisms on how the SHP2 mutation induces the neurodevelopmental defects remain elusive. Here, we report that cortical organoids (NS-COs) derived from NS-induced pluripotent stem cells (iPSCs) exhibit developmental abnormalities, especially in excitatory neurons (ENs). Although NS-COs normally develop in appearance, single-cell transcriptomic analysis represented increment of EN population and overexpression of cortical layer markers in NS-COs. Surprisingly, EN subpopulation co-expressing upper layer marker SATB2 and deep layer maker CTIP2 was enriched in NS-COs during the cortical development. In parallel with the developmental disruptions, NS-COs also exhibited reduced synaptic connectivity. Collectively, our findings suggest that perturbed cortical layer identity and impeded neuronal connectivity account for the neurological manifestations of NS.

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Upper cortical layer-driven network impairment in schizophrenia

Project description:Schizophrenia is one of the most wide-spread and complex mental disorders. To characterize the impact of schizophrenia, we performed single nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. Additionally, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most dramatic - in upper layer GABAergic neurons, including downregulation in energy metabolism and upregulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Finally, Visium spatial transcriptomics further corroborated upper layer neuron vulnerability in schizophrenia. Overall, our results point towards general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology. Study is available on bioRxiv (https://doi.org/10.1101/2020.11.17.386458) and in upcoming publication.

| EGAS00001006495 | EGA

Sliced Human Cortical Organoids for Modeling Distinct Cortical Neuronal Layer Formation

Project description:Sliced Human Cortical Organoids for Modeling Distinct Cortical Neuronal Layer Formation

| PRJNA573917 | ENA

Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity.

Project description:Retinoic acid-related orphan receptor beta (RORβ) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age in wildtype mice. Loss of RORβ delays excitatory input and disrupts gene expression and chromatin accessibility, with down-regulation of L4 and up-regulation of L5 genes, suggesting a disruption in cellular specification. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORβ, Thsd7a, is down-regulated without RORβ, and Thsd7a knock-out alone disrupts TCA organization in adult barrels.

| S-EPMC7492084 | biostudies-literature

Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity.

Project description:Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity.

| PRJNA488898 | ENA

Transcriptional changes in the primary somatosensory cortex upon sensory deprivation

Project description:Experience-dependent plasticity (EDP) is essential for anatomical and functional maturation of sensory circuits during development and can be readily studied is the rodent barrel cortex. Using this model we aimed to uncover changes on the transcriptome level and applied RNA sequencing upon altered sensory experience in juvenile mice in a cortical column and layer specific manner. From column- and layer-specific barrel cortical tissue, high quality RNA was purified and sequenced. The current dataset entails an average of 50 million paired-end reads per sample, 75 base pairs in length.

2017-08-17 | GSE90929 | GEO

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