Gene expression profilling of NEUROG2-mCherry lineage in cerebral organoids
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE277092 | GEO | 2024/12/19
REPOSITORIES: GEO
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Project description:Gene expression profilling of NEUROG2-mCherry lineage in cerebral organoids
| PRJNA1160714 | ENA
Project description:Humans exemplify gyrencephalic species with folded cerebral cortices, contrasting with lissencephalic mammals such as mice. Here we investigated how proneural genes Neurog2 and Ascl1 control cortical folding by regulating neurogenic patterns. Cortical neural progenitor cells (NPCs) stratify into four pools (proneural negative, Neurog2+, Ascl1+, double+) that are distributed evenly in mouse cortices and modular in gyrencephalic macaque cortices and pseudo-folded human cerebral organoids. Each pool has distinct developmental potentials, transcriptomes, epigenomes, and gene regulatory networks. Neurog2-Ascl1 form a bistable toggle switch double+ NPCs to prevent lineage commitment observed in single+ NPCs. Neurog2 and Ascl1 act redundantly to control neurogenic timing, with NPCs precociously depleted in Neurog2-/-;Ascl1-/- cortices. Finally, selective killing of Neurog2/Ascl1 double+ NPCs using Neurog2/Ascl1 split-Cre;Rosa-DTA transgenics breaks neurogenic symmetry in mice by locally disrupting Notch signaling, leading to cortical folding. Our findings suggest that Neurog2/Ascl1 double+ NPCs are Notch-ligand expressing ‘niche’ cells that regulate neurogenic continuity and cortical gyrification.
2021-05-26 | GSE84120 | GEO
Project description:To generate an unbiased view of changes to the retinal gene network in Neurog2 retinal mutants as well as understanding the effects of Mash1 ectopic expression in a Neurog2 retinal mutant, we generated and compared the E12.5 transcriptomes from Neurog2 heterozygote, Neurog2 mutant and Neurog2 mutant;Mash1 knock-in mice. A pair of E12.5 retinas from each biologic replicate underwent FACS sorting to isolate GFP+ cells. GFP+ cells were used to produce libraries for high throughput sequencing (n = 3 biologic replicates/genotype). Reads were aligned with BWA and Bowtie programs to the mm10 genome. Aligned reads were then analyzed for differentially expressed transcripts using the CuffDiff program in the Galaxy online bioinformatics package (www.usegalaxy.org).
2018-08-30 | GSE111666 | GEO
Project description:The proneural NEUROG2 is essential for neuronal commitment, cell cycle exit and neuronal differentiation. Characterizing genes networks regulated downstream of NEUROG2 is therefore of prime importance. To identify NEUROG2 early response genes, we combined gain of function in the neural tube with a global detection of modified transcripts using microarrays. We included in our study a mutant form of NEUROG2 (NEUROG2AQ) that cannot bind DNA and cannot trigger neurogenesis. Using this approach, we identified 942 genes modified at the onset of NEUROG2 activation. The global analysis of functions regulated by NEUROG2 allowed unmasking its rapid impact on cell cycle control. We found that NEUROG2 specifically represses a subset of cyclins acting at the G1 and S phases of the cell cycle, thereby impeding S phase re-entry. This repression occurs before modification of p27kip1, indicating that the decision to leave the cell cycle precedes the activation of this Cyclin-dependant Kinase Inhibitor. Moreover, NEUROG2 down-regulates only one of the D-type cyclins, cyclinD1, and maintaining cyclinD1 blocks the ability of the proneural to trigger cell cycle exit, without altering its capacity to trigger neuronal differentiation. The fact that NEUROG2 represses a subset but not all cell cycle regulators indicates that cell cycle exit is not an indirect consequence of neuronal differentiation but is precisely controlled by NEUROG2. Altogether our findings indicate that NEUROG2, by specifically repressing G1 and S cyclins, allows committed neuronal precursors to perform their last mitosis but blocks their re-entry in the cell cycle, thus favouring cell cycle exit. Stage HH10-11 embryos (11 to 15 somites) were electroporated with a control vector (pGIG-GFP), a NEUROG2-expressing vector (pCIGNEUROG2-GFP), or a NEUROG2AQ-expressing vector (pCIGNEUROG2AQ-GFP). For each biological replicate, neural tubes from 20 embryos were pooled for GFP+ cells collection. GFP+ cells were collected 6h later using FACS sorting (Epics Altra HSS cell sorter, Toulouse Rio platform) and processed for RNA probe preparation and hybridization on Affymetrix microarrays. For each experimental condition, four biological replicates were processed.
2012-05-04 | E-GEOD-37782 | biostudies-arrayexpress
Project description:Asymmetric neuronal expansion is thought to drive evolutionary transitions from lissencephalic to gyrencephalic cerebral cortices. We report that Neurog2 and Ascl1 proneural genes interact to sustain neurogenic continuity and lissencephaly in rodents. Using transgenic reporter mice and human cerebral organoids, we found that Neurog2 and Ascl1 expression defines a continuum of four lineage-biased neural progenitor cell (NPC) pools. Double+ NPCs, at the hierarchical apex, are least lineage-restricted due to Neurog2-Ascl1 cross-repression, and display unique features of multipotency (more open chromatin, complex gene regulatory network, G2 pausing). Strikingly, selective killing of double+ NPCs using Neurog2-Ascl1 split-Cre mice and three ‘deletor’ strains breaks neurogenic symmetry by locally disrupting Notch signaling, leading to cortical folding. Consistent with proneural genes driving discontinuous neurogenesis and folding via Notch, NEUROG2, ASCL1 and HES1 transcripts are modular in gyrencephalic macaque cortices. Neurog2/Ascl1 double+ NPCs are thus Notch-ligand expressing ‘niche’ cells that control neurogenic periodicity and cortical gyrification.
2021-07-08 | GSE151775 | GEO
Project description:The proneural NEUROG2 is essential for neuronal commitment, cell cycle exit and neuronal differentiation. Characterizing genes networks regulated downstream of NEUROG2 is therefore of prime importance. To identify NEUROG2 early response genes, we combined gain of function in the neural tube with a global detection of modified transcripts using microarrays. We included in our study a mutant form of NEUROG2 (NEUROG2AQ) that cannot bind DNA and cannot trigger neurogenesis. Using this approach, we identified 942 genes modified at the onset of NEUROG2 activation. The global analysis of functions regulated by NEUROG2 allowed unmasking its rapid impact on cell cycle control. We found that NEUROG2 specifically represses a subset of cyclins acting at the G1 and S phases of the cell cycle, thereby impeding S phase re-entry. This repression occurs before modification of p27kip1, indicating that the decision to leave the cell cycle precedes the activation of this Cyclin-dependant Kinase Inhibitor. Moreover, NEUROG2 down-regulates only one of the D-type cyclins, cyclinD1, and maintaining cyclinD1 blocks the ability of the proneural to trigger cell cycle exit, without altering its capacity to trigger neuronal differentiation. The fact that NEUROG2 represses a subset but not all cell cycle regulators indicates that cell cycle exit is not an indirect consequence of neuronal differentiation but is precisely controlled by NEUROG2. Altogether our findings indicate that NEUROG2, by specifically repressing G1 and S cyclins, allows committed neuronal precursors to perform their last mitosis but blocks their re-entry in the cell cycle, thus favouring cell cycle exit.
2012-05-05 | GSE37782 | GEO
Project description:The organoids heterogenously expressed mCherry by the lentivirus transduction were dissociated into single cells. A single mCherry- positive and -negative cell were collected and grown up to the organoids, respectivery. The difference of the gene expression profile between mCherry- positive and -negative organoids was assessd by maicroarray.
2014-07-16 | GSE59425 | GEO
Project description:The neocortex is comprised of six neuronal layers that are derived in an inside-out sequence. Neurog2, a proneural gene encoding a basic-helix-loop-helix transcription factor, is required and sufficient to specify the fate of only early-born, deep-layer neurons, despite being expressed throughout the cortical neurogenic period. To identify potential inhibitors of Neurog2 function, we used a TAP-tagging screen, identifying L3mbtl3, a histone methyl-lysine binding protein that interacts with Rnf2 in Polycomb Repressive Complex 1 (PRC1), as a novel Neurog2 interactor. We found that L3mbtl3 is co-expressed with Neurog2 and other PRC1 genes in cortical progenitors. In L3mbtl3 knock-out (KO) cortices, upper-layer neurons are generated in reduced numbers, and instead, the cortical progenitor pool is expanded. Transcriptomic analyses of L3mbtl3 KO cortices at early and mid neurogenesis revealed a striking upregulation of negative regulators of transcription, including Rest, a repressor of many neurogenic genes, and an associated downregulation of neuronal differentiation and maturation genes. Notably, transcriptomic changes occur in the absence of any changes to chromatin structure, suggesting that L3mbtl3 influences gene transcription directly and not via changes to the chromatin. Instead, L3mbtl3 represses Neurog2 transcriptional activity in vitro and blocks cortical progenitor cell maturation and neuronal migration in vivo by altering the expression of scaffold genes. L3mbtl3 is thus an essential negative regulator of cortical neurogenesis.
2021-07-06 | GSE179470 | GEO
Project description:The neocortex is comprised of six neuronal layers that are derived in an inside-out sequence. Neurog2, a proneural gene encoding a basic-helix-loop-helix transcription factor, is required and sufficient to specify the fate of only early-born, deep-layer neurons, despite being expressed throughout the cortical neurogenic period. To identify potential inhibitors of Neurog2 function, we used a TAP-tagging screen, identifying L3mbtl3, a histone methyl-lysine binding protein that interacts with Rnf2 in Polycomb Repressive Complex 1 (PRC1), as a novel Neurog2 interactor. We found that L3mbtl3 is co-expressed with Neurog2 and other PRC1 genes in cortical progenitors. In L3mbtl3 knock-out (KO) cortices, upper-layer neurons are generated in reduced numbers, and instead, the cortical progenitor pool is expanded. Transcriptomic analyses of L3mbtl3 KO cortices at early and mid neurogenesis revealed a striking upregulation of negative regulators of transcription, including Rest, a repressor of many neurogenic genes, and an associated downregulation of neuronal differentiation and maturation genes. Notably, transcriptomic changes occur in the absence of any changes to chromatin structure, suggesting that L3mbtl3 influences gene transcription directly and not via changes to the chromatin. Instead, L3mbtl3 represses Neurog2 transcriptional activity in vitro and blocks cortical progenitor cell maturation and neuronal migration in vivo by altering the expression of scaffold genes. L3mbtl3 is thus an essential negative regulator of cortical neurogenesis.
2021-07-06 | GSE179377 | GEO
Project description:Control mCherry virus (Lv13) and mouse mCherry NGFR virus (Lv16) were injected in the Wild Type mouse brain and at 3 dpi, the hippocampi of the mouse were dissected, dissociated, and mCherry positve cells were sorted by FACS for single-cell sequencing.
2023-09-12 | GSE189626 | GEO