Expression profiles in response to HMGA overexpression in late-stage neural precursor cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE41882 | GEO | 2013/02/01
SECONDARY ACCESSION(S): PRJNA178388
REPOSITORIES: GEO
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Project description:Neural precursor cells (NPCs) in the mammalian neocortex generate various neuronal and glial cell types in a developmental stage-dependent manner. Most neocortical NPCs lose their neurogenic potential after birth. We have previously shown that high mobility group A (HMGA) proteins confer the neurogenic potential on early-stage NPCs during the midgestation period, although the underlying mechanisms are not fully understood. Here we performed microarray analysis and compared expression profiles between control and HMGA2-overexpressed NPCs. Mouse neocortical neuroepithelial cells were isolated at embryonic day 11.5 and cultured as neurospheres for 9 days in vitro in the presence of fibroblast growth factor (FGF) 2 and epidermal growth factor (EGF). These cells were infected with control or HMGA2-expressing retrovirus, cultured in the presence of FGF and EGF for 3 days. Half of them were collected immediately for microarray analysis, and the other half were cultured in the absence of FGF for 12 h and then collected for microarray analysis.
2013-02-01 | E-GEOD-41882 | biostudies-arrayexpress
Project description:During development of the mammalian central nervous system (CNS), neurons and glial cells (astrocytes and oligodendrocytes) are generated from common neural precursor cells (NPCs). However, neurogenesis precedes gliogenesis, which normally commences at later stages of fetal telencephalic development. Astrocyte differentiation of mouse NPCs at embryonic day (E) 14.5 (relatively late gestation) is induced by activation of the transcription factor STAT3, whereas at E11.5 (mid-gestation) NPCs do not differentiate into astrocytes even when stimulated by STAT3-activating cytokines such as leukemia inhibitory factor (LIF). This can be explained in part by the fact that astrocyte-specific gene promoters are highly methylated in NPCs at E11.5, but other mechanisms are also likely to play a role. We therefore sought to identify genes involved in the inhibition of astrocyte differentiation of NPCs at midgestation. We first examined gene expression profiles in E11.5 and E14.5 NPCs, using Affymetrix GeneChip analysis, applying the Percellome method to normalize gene expression level. We then conducted in situ hybridization analysis for selected genes found to be highly expressed in NPCs at midgestation. Among these genes, we found that N-myc and high mobility group AT-hook 2 (Hmga2) were highly expressed in the E11.5 but not the E14.5 ventricular zone of mouse brain, where NPCs reside. Transduction of N-myc and Hmga2 by retroviruses into E14.5 NPCs, which normally differentiate into astrocytes in response to LIF, resulted in suppression of astrocyte differentiation. However, sustained expression of N-myc and Hmga2 in E11.5 NPCs failed to maintain the hypermethylated status of an astrocyte-specific gene promoter. Taken together, our data suggest that astrocyte differentiation of NPCs is regulated not only by DNA methylation but also by genes whose expression is controlled spatio-temporally during brain development. Keywords: Cell type comparison
2008-07-31 | GSE10796 | GEO
Project description:During development of the mammalian central nervous system (CNS), neurons and glial cells (astrocytes and oligodendrocytes) are generated from common neural precursor cells (NPCs). However, neurogenesis precedes gliogenesis, which normally commences at later stages of fetal telencephalic development. Astrocyte differentiation of mouse NPCs at embryonic day (E) 14.5 (relatively late gestation) is induced by activation of the transcription factor STAT3, whereas at E11.5 (mid-gestation) NPCs do not differentiate into astrocytes even when stimulated by STAT3-activating cytokines such as leukemia inhibitory factor (LIF). This can be explained in part by the fact that astrocyte-specific gene promoters are highly methylated in NPCs at E11.5, but other mechanisms are also likely to play a role. We therefore sought to identify genes involved in the inhibition of astrocyte differentiation of NPCs at midgestation. We first examined gene expression profiles in E11.5 and E14.5 NPCs, using Affymetrix GeneChip analysis, applying the Percellome method to normalize gene expression level. We then conducted in situ hybridization analysis for selected genes found to be highly expressed in NPCs at midgestation. Among these genes, we found that N-myc and high mobility group AT-hook 2 (Hmga2) were highly expressed in the E11.5 but not the E14.5 ventricular zone of mouse brain, where NPCs reside. Transduction of N-myc and Hmga2 by retroviruses into E14.5 NPCs, which normally differentiate into astrocytes in response to LIF, resulted in suppression of astrocyte differentiation. However, sustained expression of N-myc and Hmga2 in E11.5 NPCs failed to maintain the hypermethylated status of an astrocyte-specific gene promoter. Taken together, our data suggest that astrocyte differentiation of NPCs is regulated not only by DNA methylation but also by genes whose expression is controlled spatio-temporally during brain development. Experiment Overall Design: Neuroepithelial cells(NPCs) were prepared from telencephalons of E11.5 and E14.5 mice and cultured in N2-supplemented Dulbecco's Modified Eagle's Medium with F12 (GIBCO) containing 10 ng/ml basic FGF (R&D Systems) (N2/DMEM/F12/bFGF) on culture dishes (Nunc) or chamber slide (Nunc) which had been precoated with poly-L-ornithine (Sigma) and fibronectin (Sigma). E11.5 NPCs were cultured for one day and E14.5 NPCs were for four days.
2008-10-20 | E-GEOD-10796 | biostudies-arrayexpress
Project description:Down syndrome neurophenotypes are characterized by mental retardation and a decreased brain volume. In order to identify whether deficits in proliferation, differentiation or survival could be responsible for this phenotype, neural precursor cells (NPCs) were isolated from the developing E14 neocortex of Down syndrome partial trisomy Ts1Cje mice and euploid (WT) littermates. Proliferation, cell differentiation and cell death assays revealed that Ts1Cje NPCs proliferated at a slower rate, due to a longer cell cycle and that a greater number of cells were positive for glial fibrillary acidic protein. An increase in Ts1Cje NPC cell death was also noted. Gene expression profiling was conducted on RNA extracted from Ts1Cje and WT NPCs. Approximately 54% of triploid gene expression ratios were significantly greater than the expected diploid gene ratio of 1.0. A number of diploid genes associated with differentiation, glial function and proliferation were dysregulated. The evidence points to a delay in cellular cycling that could exert stress on the NPC population, which might result in cellular death and a mobilization of glial cell survival responses. Importantly, these phenotypic changes, which mimic those seen in Down syndrome individuals, do not require over-expression of amyloid precursor protein (App) or soluble superoxide dismutase 1 (Sod1). In conclusion, early developmental proliferation deficits in Down syndrome result in secondary morphological changes that can impact on cognitive development and function. Keywords: Down syndrome, Neocortical precursor cells, transcriptome, proliferation Neural precursor cells (NPCs) were isolated from mouse E14 neocortex of Down syndrome Ts1Cje mice and euploid littermates. We compared gene expression profiles from trisomic and wild-type cells using pangenomic microarrays.
2010-05-19 | E-GEOD-9805 | biostudies-arrayexpress
Project description:Neocortical projection neurons of mammalian brains are largely direct daughters of intermediate progenitors (IP), which are progenies of radial glial cells (RG). The maintenance of the RG pool, production and expansion of IPs are essential for neocortical formation during development, as well as neocortical expansion during evolution. Here we characterized an epigenetic circuit that controls precise neurogenic programming of the neocortex. The circuit comprises a long non-coding RNA – LncBAR and the SWI/SNF (BAF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production of RGCs, but hampers neurogenic division and lengthens the cell-cycle durations of IPs during mid-later cortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage causes fewer adult neural stem cells at the subventricular zone, leading to compromised adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the SWI/SNF (BAF) chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with and the genomic locus of, and suppresses the expression of Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 re-expression in LncBAR-knockout neural precursors reversed compromised neurogenic divisions of IPCs. Together, we revealed a previously unidentified epigenetic machinery to control neurogenesis of neural precursors.
2021-10-27 | GSE169165 | GEO
Project description:Neocortical projection neurons of mammalian brains are largely direct daughters of intermediate progenitors (IP), which are progenies of radial glial cells (RG). The maintenance of the RG pool, production and expansion of IPs are essential for neocortical formation during development, as well as neocortical expansion during evolution. Here we characterized an epigenetic circuit that controls precise neurogenic programming of the neocortex. The circuit comprises a long non-coding RNA – LncBAR and the SWI/SNF (BAF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production of RGCs, but hampers neurogenic division and lengthens the cell-cycle durations of IPs during mid-later cortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage causes fewer adult neural stem cells at the subventricular zone, leading to compromised adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the SWI/SNF (BAF) chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with and the genomic locus of, and suppresses the expression of Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 re-expression in LncBAR-knockout neural precursors reversed compromised neurogenic divisions of IPCs. Together, we revealed a previously unidentified epigenetic machinery to control neurogenesis of neural precursors.
2021-10-27 | GSE169164 | GEO
Project description:The neocortex, the center for higher brain function, first emerged in mammals and has become massively expanded and folded in humans, constituting almost half the volume of the human brain. Primary microcephaly, a developmental disorder in which the brain is smaller than normal at birth, mainly results from there being fewer neurons in the neocortex because of defects in neural progenitor cells (NPCs). Outer radial glia (oRGs), NPCs that are abundant in gyrencephalic species but rare in lisencephalic species, are thought to play key roles in the expansion and folding of the neocortex. However, how oRGs expand, whether they are necessary for neocortical folding, and whether defects in oRGs cause microcephaly remain important questions in the study of brain development, evolution, and disease. Here, we show that oRG expansion in mice, ferrets, and human cerebral organoids requires cyclin-dependent kinase 6 (CDK6), the mutation of which causes primary microcephaly via an unknown mechanism. In a mouse model in which increased Hedgehog signaling expands oRGs and intermediate progenitor cells and induces neocortical folding, CDK6 loss selectively decreased oRGs and abolished neocortical folding. Remarkably, this function of CDK6 in oRG expansion did not require its kinase activity, was not shared by the highly similar CDK4 and CDK2, and was disrupted by the mutation causing microcephaly. Therefore, our results indicate that CDK6 is conserved to promote oRG expansion; that oRGs are necessary for neocortical folding; and that defects in oRG expansion may cause primary microcephaly.
2022-08-31 | GSE211990 | GEO
Project description:The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here we present genome-wide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs available for future exploration. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes. We used catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.
2017-08-03 | GSE90694 | GEO
Project description:The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here we present genome-wide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs available for future exploration. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes. We used catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.
2017-08-03 | GSE90447 | GEO
Project description:We examined the dynamic changes of H3K27me3 and gene expression in neocortical neural stem cells directly isolated from various stages of embryonic brains. ChIP-seq of HMGA2 protein in the early stage of neural stem cell, and transcriptome analysis of Ring1A-/-;Ring1Bf/f and Ring1A-/-;Ring1B-/- were also performed.
2023-09-06 | GSE86461 | GEO