Genetic and epigenetic coordination of cortical interneuron development
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ABSTRACT:
PROVIDER: PRJNA693723 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR13454144_1.fastq.gz | Fastqsanger.gz | |||
| SRR13454144_2.fastq.gz | Fastqsanger.gz | |||
| SRR13454145_1.fastq.gz | Fastqsanger.gz | |||
| SRR13454145_2.fastq.gz | Fastqsanger.gz |
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Project description:One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons1-3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence4-11. This makes them an attractive model for studying the generation of cell diversity. Here we examine how developmental changes in transcription and chromatin structure enable these cells to acquire distinct identities in the mouse cortex. Generic interneuron features are first detected upon cell cycle exit through the opening of chromatin at distal elements. By constructing cell-type-specific gene regulatory networks, we observed that parvalbumin- and somatostatin-positive cells initiate distinct programs upon settling within the cortex. We used these networks to model the differential transcriptional requirement of a shared regulator, Mef2c, and confirmed the accuracy of our predictions through experimental loss-of-function experiments. We therefore reveal how a common molecular program diverges to enable these neuronal subtypes to acquire highly specialized properties by adulthood. Our methods provide a framework for examining the emergence of cellular diversity, as well as for quantifying and predicting the effect of candidate genes on cell-type-specific development.
| S-EPMC9316417 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-09-22 | GSE165233 | GEO
Project description:ERK1/2 signaling and cortical interneuron development
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Project description:GABAergic interneuron in the cortex comprise a very heterogenous group. and it is critical to identify discrete interneuron types to understand how their contributions to behavior can be modulated by external and internal cues. However, molecular difinition of these interneuron cell groups has been difficult. Comparative analysis of different interneuron subtypes can provide us new candidate marker genes which could target more specific interneu?on cell group. Here we identify oxytocin responsive novel class of interneuron through our comparative analysis. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from Nek7, Dlx1, Cort, Htr3a, Oxtr expressing cortical interneurons. We show that Oxtr expressing cells are a subtype of somatostatin positive interneurons. Three independent TRAP replicates were collected and total RNA from the immunoprecipitates or flow-through (input) whole cortex lysates were amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the Nek7 BAC labels non-neuronal cells, we recommend to delete astrocytes and oligodendrocytes genes from the list using GSE13379 data.
2014-10-07 | E-GEOD-56996 | biostudies-arrayexpress
Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells (hESCs) to study gene expression changes during this process, to identify regulatory networks critical to cortical interneuron development. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like progenitors), day 35 (immature interneurons), and day 60 (mature interneurons).
2024-04-18 | GSE239396 | GEO
Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells to study chromatin state changes during cortical interneuron development. This allows for the identification of cis-regulatory elements and transcription factors which play important roles in this process. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like (MGE) progenitors), day 35 (immature interneurons), and day 60 (mature interneurons). Day 15 dorsal telencephalic cortical-like neural progenitors were also obtained by using a dual Smad inhibition protocol for comparison with ventral telencephalic MGE-like progenitors.
2024-04-18 | GSE239400 | GEO
Project description:Interneurons navigate along multiple tangential paths to settle into appropriate cortical layer. They undergo saltatory migration, which is paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. However, it remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes deglutamylation, is a pivotal regulator of pausing of cortical interneurons. Moreover, we show that pausing during migration controls the flow of interneurons invading the cortex by generating heterogeinity in movement at the population level. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also secondarily impairs the generation of age-matched upper layer projection neurons.
2018-02-14 | PXD006397 | Pride
Project description:GABAergic interneuron in the cortex comprise a very heterogenous group. and it is critical to identify discrete interneuron types to understand how their contributions to behavior can be modulated by external and internal cues. However, molecular difinition of these interneuron cell groups has been difficult. Comparative analysis of different interneuron subtypes can provide us new candidate marker genes which could target more specific interneuｒon cell group. Here we identify oxytocin responsive novel class of interneuron through our comparative analysis. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from Nek7, Dlx1, Cort, Htr3a, Oxtr expressing cortical interneurons. We show that Oxtr expressing cells are a subtype of somatostatin positive interneurons.
2014-10-07 | GSE56996 | GEO
Project description:In the mammalian cortex, about 60% of GABAergic interneurons, mainly including parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons are generated from the medial ganglionic eminence (MGE) in the subpallium and tangentially migrate to the cortex. Here we analyze the role of the Sp9 transcription factor in regulating the development of MGE-derived cortical interneurons. We show that SP9 is widely expressed in the MGE subventricular zone (SVZ) and in MGE-derived migrating interneurons. By analyzing Sp9 null and conditional mutant mice, we demonstrate that Sp9 promotes MGE progenitor proliferation in the SVZ and is required for the normal patterning of tangential migration and the laminar distribution of MGE-derived cortical GABAergic interneurons. Loss of Sp9 function results in a ~50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. Finally, we provide evidence that Sp9 regulates MGE derived cortical interneuron development through promoting expression of the Lhx6 and Lhx8 transcription factors.
2017-05-19 | GSE99049 | GEO
Project description:Organoid techniques provide unique platforms to model brain development and neurological disorders. While organoids recapitulating corticogenesis were established, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, remains to be developed. Here, we describe a system to generate MGE or cortex-specific organoids from human pluripotent stem cells. These organoids recapitulate the developments of MGE and cortex domains respectively. Population and single-cell transcriptomic profiling revealed transcriptional dynamics and lineage productions during MGE and cortical organoids development. Chromatin accessibility landscapes were found to be involved in this process. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, we applied fusion organoids as a model to investigate human interneuron migration. Together, our study provides a new platform for generating domain-specific brain organoids, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development.
2017-07-21 | GSE97880 | GEO