The dynamic landscape of open chromatin during human cortical neurogenesis
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ABSTRACT:
PROVIDER: PRJNA399225 | ENA |
REPOSITORIES: ENA
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Project description:The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs) whose asymmetric division give birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Our data suggest that interfering with codon translation speed triggers endoplasmic reticulum stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a hitherto unrecognized contribution of UPR to cell fate acquisition during mammalian brain development. Ribosome profiling and RNA-Seq of forebrains from E14.5 mouse embryos from wild type animals and mutants carrying a conditional knockout of ELP3 in cortical progenitors
2015-12-11 | E-GEOD-74683 | biostudies-arrayexpress
Project description:Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. We link distal regulatory elements (DREs) to their cognate gene(s) together with chromatin interaction data and show that target genes of human-gained enhancers (HGEs) regulate cortical neurogenesis and are enriched in outer radial glia, a cell type linked to human cortical evolution. We experimentally validate the regulatory effects of predicted enhancers for FGFR2 and EOMES. We observe that common genetic variants associated with educational attainment, risk for neuropsychiatric disease, and intracranial volume are enriched within regulatory elements involved in cortical neurogenesis, demonstrating the importance of this early developmental process for adult human cognitive function.
| S-EPMC5924568 | biostudies-literature
Project description:The dynamic landscape of open chromatin during human cortical neurogenesis
| PRJNA399226 | ENA
Project description:Postnatal brain neurogenesis in mammals is believed to be restricted to rare germinative remnants of the neuroepithelium. In this study, we discovered that, in the postnatal brain, a subset of embryonically derived progenitors is present in meningeal substructures. These cells migrate from the meningeal substructures to the retrosplenial and visual motor cortex and differentiate into (electrically) functional integrated neurons. Lineage tracing analysis revealed that this subset of neural progenitors originate largely from PDGFR+ cells. PDGFR-derived cells differentiate mostly into Satb2+ neurons in cortical layers I-IV. Thus, a reservoir of embryonically derived progenitors in the meninges contributes to postnatal cerebral cortical neurogenesis.
2016-11-23 | E-MTAB-4951 | biostudies-arrayexpress
Project description:The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs) whose asymmetric division give birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Our data suggest that interfering with codon translation speed triggers endoplasmic reticulum stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a hitherto unrecognized contribution of UPR to cell fate acquisition during mammalian brain development.
2015-12-11 | GSE74683 | GEO
Project description:We aim to profile the dynamic changes of chromatin accessibility (openness) to transcription factors during cortical neuron differentiation from human iPSCs. We used ATAC-seq to map open chromatins in iPSCs, neural stem cells (NSCs) at day 27 and day 33 of neural induction (designated as iN-d30 for simplicity), and neurons at day 41 (iN-d41). We found that there were robust dynamic changes of open chromatins that are corresponding to cell stage-specific gene function both at genome-wide level and at individual loci of interest to neurodevelopment and psychiatric disorders, with NSC (iN-d30) gaining most (89%) of the neuron specific open chromatin peaks. Open chromatin peaks shared by different cell stages were overrepresented in core promoters, while the peaks specific to each cell stage or showing dynamic change of openness were enriched in introns and intergenic sequences. The dynamic change of open chromatins is orchestrated by specific sets of transcription factors (TFs) in each cell stage, providing epigenomic support the central role of NEUROD1 and NEUROG2 in cortical neuron differentiation.
2017-07-27 | GSE70823 | GEO
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined mRNA expression profiles using mouse mRNA microarray (Illumina MouseWG-6 v2). Comparison of E13 and E16 mRNA expression profiles allowed us to identify regulatory gene networks for maintaining stage specific homeostasis of BPs throughout neurogenesis. FACS isolated BPs at E13 and E16 mouse brain cortex were used for microarray analyses. Six biological replicates (embryonic cortex from three different litters) for E13 and five biological replicates (embryonic cortex from three different litters) for E16 were analysed.
2014-05-01 | E-GEOD-45450 | biostudies-arrayexpress
Project description:Meningeal cells contribute to postnatal cortical neurogenesis.
| PRJEB14890 | ENA
Project description:Apical progenitors remain multipotent throughout cortical neurogenesis
| PRJNA505836 | ENA
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined miRNA expression profiles using mouse miRNA microarray (Agilent).Comparison of E13 and E16 microRNA expression profiles allowed us to identify regulatory mechanisms for maintaining stage specific homeostasis of BPs. FACS isolated BPs at E13 and E16 mouse brain cortex were used for miRNA microarray analyses. Four biological replicates (embryonic cortex from three different litters) for each group (E13 or E16) were analysed.
2014-05-01 | E-GEOD-45449 | biostudies-arrayexpress