Spatial transcriptomic data of P5 mouse cortical somatostatin neurons
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PROVIDER: PRJNA1035530 | ENA |
REPOSITORIES: ENA
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Project description:The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge through the implementation of different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons, as they represent a relatively small proportion of all cortical cells, migrate tangentially from their embryonic origin to the cerebral cortex, and have a protracted development. Here we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells, the most diverse subclass of inhibitory neurons in the mouse cerebral cortex. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is further refined during early postanal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons. Thus, the diversification of SST+ inhibitory neurons involves a temporal cascade of unique molecular programs driving their divergent developmental trajectories.
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Project description:This SuperSeries is composed of the following subset Series: GSE24440: Sprouting transcriptome in cortical neurons: young GSE24441: Sprouting transcriptome in cortical neurons: aged Refer to individual Series
2010-11-15 | E-GEOD-24442 | biostudies-arrayexpress
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
Project description:Total RNA-sequencing of FACs isolated nucleus accumbens somatostatin interneuron nuclei Somatostatin interneuron loss in multiple cortical brain regions has been observed postmortem in humans with several neuropsychiatric disorders and their loss is proposed to underlie some common pathological changes in circuit function across numerous syndromes. However, somatostatin interneurons in the nucleus accumbens (NAc), a key brain reward region, remain poorly understood due to the fact that these cells account for <1% of NAc neurons. Here, we used Flouresence activated cell sorting to isolate nuclei of somatostatin-expressing interneurons in the Nucleus Accumbens from individual SST-TLG498 reporter mice that express membrane bound EGFP-F specifically in somatostatin-expressing neurons. We then performed cell-type specific Total RNA-sequencing to characterize the entire transcriptome of NAc somatostatin interneurons after repeated exposure (7 days) to either saline or cocaine. We identified a wide variety of coding and non-coding transcripts that were expressed at high levels and were differentially expressed between saline and cocaine treated mice. Repeated cocaine administration induces transcriptome-wide changes in gene expression within NAc somatostatin interneurons, with particular regulation of transcripts related to neural plasticity. Our results identify alterations in NAc induced by cocaine in a sparse population of somatostatin interneurons, and illustrate the value of studying brain diseases using cell type-specific whole transcriptome RNA-sequencing to identify novel neurpathophysiology.
2018-07-03 | GSE116484 | GEO
Project description:Gene expression from icas9 human iPSC derived cortical neurons treated with and without doxycycline
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Project description:Cortical interneuron diversity arises from the interplay of intrinsic developmental patterning and local extrinsic cues. While individual genetic programs underlying cardinal cell type identity are established in immature neurons prior to integration into cortical circuits, it remains unclear whether distinct interneuron subtype identities are pre-established, and if so, how their identity is maintained prior to circuit integration. Sox6 is a transcription factor with an established role in the maturation of interneurons derived from the medial ganglionic eminence and cell-type specification in other neuronal and non-neuronal cells. To determine a possible role in maintaining cortical somatostatin-expressing (Sst+) interneuron subtype identity, we conditionally removed Sox6 (Sox6-cKO) in migrating Sst+ interneurons and assessed the effects on their mature identity. In adolescent animals, five of eight molecular Sst+ subtypes were nearly absent in the cortex of Sox6-cKO mice. This reduced subtype diversity was not due to a decrease in the overall number of Sst+ interneurons and cells displayed electrophysiological maturity and expressed genes enriched within the broad class of Sst+ interneurons. Furthermore, we show that at embryonic day 18.5, prior to cortical integration, mature Sst+ cell subtype identity could already be inferred in both control and Sox6-cKO cortices, suggesting that the loss in subtype diversity observed in the mature cortex is due to a disrupted subtype maintenance. Importantly, Sox6 removal at postnatal day 7, after Sst+ interneurons have finished migrating and begun integration into the network, did not disrupt marker expression of Sst+ subtypes in the mature cortex. Therefore, Sox6 is necessary during this migratory phase for maintenance of Sst+ subtypes identity, indicating that subtype maintenance requires active transcriptional programs during migration.
2023-08-25 | GSE233791 | GEO
Project description:Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration
| PRJNA977997 | ENA
Project description:Complementary networks of cortical somatostatin interneurons enforce layer specific control
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Project description:E18 embryonic rat cortical neurons cultured in vitro are infected with lentivirus expressing control or PHF6shRNA-2, and harvested 5 days after infection pLL3.7 lentivirus expressing control or PHF6shRNA-2 was generated in 293T cells and concentrated using ultracentrifuge. In vitro cultured cortical neurons were infected and RNA was harvested 5 days after infection. PHF6 knockdown was validated by QPCR before sample was processed for microarray analysis.
2013-08-01 | E-GEOD-45953 | biostudies-arrayexpress