Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174341 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Evolution of the mammalian brain encompassed a remarkable increase in size of cerebral cortex, including tangential and radial expansion, but the mechanisms underlying these key parameters are still largely unknown. Here, we identified the novel DNA associated protein TRNP1 as a regulator of cerebral cortical expansion in both these dimensions. Gain and loss of function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion, while lower levels promote radial expansion resulting in a potent increase in the generation of intermediate progenitors and outer radial glial cells resulting in folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences also in the cerebral cortex of human fetuses anticipating radial or tangential expansion respectively. Thus, the dynamic regulation of TRNP1 is critical to regulate tangential and radial expansion of the cerebral cortex in mammals. We performed gene expression microarray analysis on embryonic mouse cerebral cortex derived from Trnp1 knockdown and control animals.
2013-04-26 | E-GEOD-40582 | biostudies-arrayexpress
Project description:Evolution of the mammalian brain encompassed a remarkable increase in size of cerebral cortex, including tangential and radial expansion, but the mechanisms underlying these key parameters are still largely unknown. Here, we identified the novel DNA associated protein TRNP1 as a regulator of cerebral cortical expansion in both these dimensions. Gain and loss of function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion, while lower levels promote radial expansion resulting in a potent increase in the generation of intermediate progenitors and outer radial glial cells resulting in folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences also in the cerebral cortex of human fetuses anticipating radial or tangential expansion respectively. Thus, the dynamic regulation of TRNP1 is critical to regulate tangential and radial expansion of the cerebral cortex in mammals.
2013-04-26 | GSE40582 | GEO
Project description:Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we find that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 results in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 results in enhanced formation of gyri. Single cell transcriptomics and simulations suggest that changes in adhesive properties of cortical neurons, their proportions and densities in the cortical plate, combined with lateral dispersion during their radial migration are important folding parameters. These results identify key developmental mechanisms that cooperate to promote cortical gyrification
2025-05-20 | GSE267391 | GEO
Project description:Since the discovery of radial glia as the source of neurons, their heterogeneity in regard to neurogenesis has been described by clonal and time-lapse analysis in vitro. However, the molecular determinants specifying neurogenic radial glia differently from radial glia that mostly self-renew remain ill-defined. Here, we isolated two radial glial subsets that co-exist at mid-neurogenesis in the developing cerebral cortex and their immediate progeny. While one subset generates neurons directly, the other is largely non-neurogenic but also gives rise to Tbr2-positive basal precursors, thereby contributing indirectly to neurogenesis. Isolation of ; these distinct radial glia subtypes allowed determining interesting differences in their transcriptome. These transcriptomes were also strikingly different from the transcriptome of radial glia isolated at the end of neurogenesis. This analysis therefore identifies, for the first time, the lineage origin of basal progenitors and the molecular differences of this lineage in comparison to directly neurogenic and gliogenic radial glia. Experiment Overall Design: Comparison of radial glial subtypes
2008-06-18 | E-GEOD-8034 | biostudies-arrayexpress
Project description:The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans, but virtually absent in rodents, called â??outer radial gliaâ?? (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined cell type-specific sorting with transcriptome-wide RNA-sequencing to identify genes enriched in human ORG, including targets of the transcription factor Neurogenin, and previously uncharacterized, evolutionarily dynamic, long noncoding RNAs. Single-cell transcriptional profiling of human, ferret, and mouse progenitors showed that more human RGC co-express proneural Neurogenin targets than in ferret or mouse, suggesting greater self-renewal of neuronal lineage-committed progenitors in humans. Finally, we show that activating the Neurogenin pathway in ferret RGC promotes delamination and outward migration. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors. Three biological replicates of human late mid-fetal cortex (18 to 19 weeks of gestation) were dissociated and immunolabeled. Apical and outer radial glial cells were purified by FACS and compared to an immunonegative population, predominantly neurons.
2015-02-24 | E-GEOD-66217 | biostudies-arrayexpress
Project description:Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development. 18 total samples consisting of three biological replicates each of flow sorted embryonic spinal cord Aldh1l1-GFP positive cells and whole cord, spanning the radial glial to astrocyte transition
2014-06-19 | E-GEOD-58614 | biostudies-arrayexpress
Project description:PNPLA8, one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological conditions through the maintenance of membrane phospholipids. However, little is known about its role in brain development. Here, we report 14 individuals from 12 unrelated families with biallelic ultra-rare variants in PNPLA8 presenting with a wide spectrum of clinical features ranging from developmental and epileptic-dyskinetic encephalopathy (DEDE) to progressive movement disorders and no phenotype depending on the variants and their positions. Complete loss of PNPLA8 was associated with the severe end of the spectrum showing DEDE manifestations and congenital or progressive microcephaly. Using cerebral organoids generated from human induced pluripotent stem cells (iPSCs), we found that loss of PNPLA8 reduces the abundance of basal radial glial cells (bRGCs) and upper-layer neurons. By spatial transcriptomic analysis targeting apical radial glial cells (aRGCs), we found the downregulation of bRGC-related gene sets in patient-derived cerebral organoids. Lipidomic analysis revealed a decrease in the amount of lysophosphatidic acid, lysophosphatidylethanolamine, and phosphatidic acid, indicative of the disturbed phospholipid metabolism in PNPLA8 knockout neural progenitor cells. Our data suggest that PNPLA8 has a critical role in the bRGC-mediated expansion of the developing human cortex by regulating the fate commitment of aRGCs.ナカセンセイキニュウ
2023-05-03 | GSE229956 | GEO
Project description:PNPLA8, one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological conditions through the maintenance of membrane phospholipids. However, little is known about its role in brain development. Here, we report 14 individuals from 12 unrelated families with biallelic ultra-rare variants in PNPLA8 presenting with a wide spectrum of clinical features ranging from developmental and epileptic-dyskinetic encephalopathy (DEDE) to progressive movement disorders and no phenotype depending on the variants and their positions. Complete loss of PNPLA8 was associated with the severe end of the spectrum showing DEDE manifestations and congenital or progressive microcephaly. Using cerebral organoids generated from human induced pluripotent stem cells (iPSCs), we found that loss of PNPLA8 reduces the abundance of basal radial glial cells (bRGCs) and upper-layer neurons. By spatial transcriptomic analysis targeting apical radial glial cells (aRGCs), we found the downregulation of bRGC-related gene sets in patient-derived cerebral organoids. Lipidomic analysis revealed a decrease in the amount of lysophosphatidic acid, lysophosphatidylethanolamine, and phosphatidic acid, indicative of the disturbed phospholipid metabolism in PNPLA8 knockout neural progenitor cells. Our data suggest that PNPLA8 has a critical role in the bRGC-mediated expansion of the developing human cortex by regulating the fate commitment of aRGCs.
2024-03-05 | GSE248252 | GEO
Project description:Basal radial glial cells (bRGs) are neural progenitors enriched in primates and humans and were proposed to contribute to the expansion of neurons during cortical development in gyrencephalic species. Shortly after their generation, bRGs delaminate towards the outer subventricular zone, where they divide multiple times before differentiation. Thus, the regulation of bRGs generation could be essential for the establishment of correct gyrification within the human cortex. Here, we study the role of LGALS3BP, a secreted protein whose RNA expression is enriched in bRGs. By using cerebral organoids, human fetal tissues and mice, we show that manipulation of LGALS3BP regulated bRG generation. Additionally, individuals with unique de novo variants in LGALS3BP demonstrate abnormal gyrification and thickness at multiple sites over their cortex. Single-cell-RNA-sequencing and proteomics reveal the extracellular matrix involvement in the LGALS3BP mediated mechanisms. We find that LGALS3BP is required for bRGs delamination and influences corticogenesis and gyrification in humans.
2021-10-26 | PXD015878 | Pride
Project description:Cortical development involves rapid progenitor expansion and cell diversification that is likely supported by tightly regulated metabolic programs, yet these programs, particularly in human development remain largely uncharacterized. Here, we generated a metabolic atlas of the early human cortex using primary tissue and stem cell-derived cortical organoids. Across developmental stages, we observed dynamic changes in core metabolic functions, including an unexpected increase in glycolysis and pentose phosphate pathway (PPP) activity during late neurogenesis. Manipulation of glucose availability in cortical organoids altered progenitor and neuronal composition, increasing outer radial glia and inhibitory neurons populations. Pharmacological and genetic inhibition of PPP enzymes recapitulated these cell fate changes and promoted radial glial maturation. Ribose was sufficient to rescue the radial glia gene expression changes, revert organoid cell type composition, and restore the levels of ATP and hypotaurine. These data identify a critical role for the PPP in modulating radial glia cell fate specification and generate a resource for future exploration of additional metabolic pathways in human cortical development.
2026-03-01 | GSE292425 | GEO