Single-cell ATAC-seq of developing cortical interneurons.
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ABSTRACT:
PROVIDER: PRJNA693000 | ENA |
REPOSITORIES: ENA
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Project description:Single-cell ATAC-sequencing of cortical GABAergic interneurons to characterize the chromatin landscapes of these cells at several timepoints across development - from their origins in the ganglionic eminences, upon migration to the cortex, settling in cortical laminae, and through maturation.
2021-09-22 | GSE165031 | GEO
Project description:Single-cell RNA-seq of developing cortical interneurons
| PRJNA691232 | ENA
Project description:Single-cell RNA-sequencing of cortical GABAergic interneurons to characterize their transcriptional profiles at several timepoints across development - from their origins in the ganglionic eminences, upon migration to the cortex, settling in cortical laminae, and through maturation.
2021-09-22 | GSE164570 | GEO
Project description:Malformations of cortical development are the underlying eitiology of many cases of Mental Retardation and Epilepsy. Subtle, below the resolution of current MRI, cortical dysplasias are probably involved in many cases of MR, Epilepsy and Autism for which no diagnosis can currently be made. Therefore, understanding the process of cortical development will be vital in diagnosing and eventual treatment of many patients with these conditions. More specifically, the cortex forms from two major populations of neuroblasts which reach their final destination in the cortex by differerent mechanisms. One is radial migration from ventricular neuroblasts to the cortical plate. These cells are excititory projection neurons and glia. The second pathway is from the ventral ganglionic eminences and tangential migration of the interneuronal population of primarily inhibitory neurons. Much less is known about the control of the latter process, and many of these currently undiagnosed subtle malformations may stem from abnormalities of this tangential migration. This project focuses on the understanding the control of the tangentially migrating inhibitory interneurons. We aim to uncover the transcriptional differences between two distinct neuronal populations, GFP positive cells in the ganglionic emience and GFP positive cells within the cortical plate, in order to understand the genetic control of tangential migration. We will acomplish this aim by targeting two different labeled transcripts againts the affymetrix mouse genome arrays. We hypothesis that there will be distinct differences in mRNA transcription profiles between the ganglionic eminence and cortical plate within developing interneurons. The differences in transcript profiles will be genes that regulate the migration and differentiation of these developing neurons. Transgenic mice have been generated which express green flourscent protien (GFP) based on the activity of the Dlx 5-6 promotor. Dlx 5-6 are highly regulated genes, and are expressed only in developing interneurons with in the embryonic brain. The expression of this gene begins at around E8 within the medial and lateral ganglionic eminence (GE) and then remain present as cells born within these regions migrate out into the developing cortex. Therefore, we can take advantage of these mice by harvesting embryos at a midpoint in their development (E13.5-14.5) and dissect out GFP positive cells from the ganglionic eminence and from the cortical plate. In order to obtain enough cells to extract sufficent mRNA, we have choosen to perform microdisction of the entire GE and entire cortical plate then break up the tissue into single cell suspension and Florescent activated cell sort (FACs) the populations of GFP + and GFP - cells. We then will extract the total RNA from the GFP postive cell populations using a Trizol based method and purify the RNA with a Quiagen column purification method. The purified RNA will then be amplified using the Affymetrix 1 or 2 round T7 based amplification procedure in order to generate the microgram quantities of labelled cRNA. The labelled biotin cRNA will be sent to the microarray consortium for hybridization againt the Affy mouse genome chip. Three embryos will be pooled in order to obtain sufficent RNA and 6 GFP positive GE and cortical plate samples will be used. The six replicates will be obtained from at least 3 different pregnant mice.
2008-06-14 | E-GEOD-5817 | biostudies-arrayexpress
Project description:In the mammalian cerebral cortex, the developmental events governing the allocation of different classes of inhibitory neurons into distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 is upregulated in serotonin receptor 3a-expressing (HTR3A) cortical interneurons (hINs) as they invade the cortical plate and that it regulates their laminar allocation to superficial cortical layers. We find that the PlexinA4 ligand Semaphorin3A acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that Semaphorin3A specifically controls their laminar positioning through PlexinA4. We identify that deep layer interneurons constitute a major source of Semaphorin3A in the developing cortex and demonstrate that cell-type specific genetic deletion of Semaphorin3A in these interneurons specifically affects the laminar allocation of hINs. These data demonstrate that in the neocortex, deep layer interneurons control the laminar allocation of hINs into superficial layers.
2021-01-19 | GSE152271 | GEO
Project description:Developmental diversification of cortical inhibitory interneurons
| PRJNA411832 | ENA
Project description:Our group has reported that the histone methyltransferase DOT1L is necessary for proper cortical plate development and layer distribution of glutamatergic neurons, however, its specific role on cortical interneuron development has not yet been explored. Here, we demonstrate that DOT1L affects interneuron development in a cell-autonomous manner. Deletion of Dot1l in MGE-derived interneuron precursor cells results in an overall reduction and altered distribution of GABAergic interneurons in the cortical plate at postnatal day (P) 0. Furthermore, we observed an altered proportion of GABAergic interneurons in the cortex and striatum at P21 with a significant decrease in Parvalbumin (PVALB)-expressing interneurons. Altogether, our results indicate that reduced numbers of cortical interneurons upon DOT1L deletion results from altered postmitotic differentiation/maturation.
2023-08-01 | GSE221994 | GEO
Project description:Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons.
2018-10-12 | GSE119998 | GEO
Project description:While epigenetic modifications are critical for cell state changes throughout development, a detailed characterization of chromatin accessibility during neurogenesis has not been explored. We collected single-cell chromatin accessibility profiles of ~40,000 cells from 4 distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many of which were restricted to distinct progenitor cell types or brain regions. By integrating snATAC-Seq and transcriptome data, we characterized changes of chromatin accessibility at enhancers and promoters that were tightly coupled to transcript abundance throughout neurodevelopment. Integrating our chromatin accessibility profiles from embryonic and adult interneurons with the iPSYCH2012 GWAS dataset revealed several disease-associated polymorphisms overlapped accessible regions in embryonic cells and MGE-derived mature interneurons. These findings highlight the coordination between chromatin accessibility and gene expression as neural progenitors mature during embryogenesis, and open the door for future studies to define critical enhancer-promoter interactions that direct cell fate decisions.
2021-12-31 | GSE167048 | GEO
Project description:Single nuclei ATAC-seq (10X Genomics Chromium) of FACS enriched cortical and hippocampal interneurons from P30 mouse brains
| PRJNA702792 | ENA