Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1213291 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The scRNA-seq analysis of 75 day old human cerebral organoids grown at the air-liquid interface (ALI-COs) reveals six well-defined major clusters. Cell-type and maturity markers define a (1) distinct population of deep layer subcortical projection neurons, (2) upper layer intracortical (callosal) projection neurons and intermediate progenitors, (3) ventricular and subventricular zone radial glial cells, (4) more mature upper and deep layer neurons, (5) interneurons and (6) actively dividing cells with intermediate progenitor and radial glia markers. In addition, the gene expression profile of these clusters corresponds with their expected functional characteristics appropriate to their maturity. Altogether, our data reflect a full repertoire of cortical neuronal and progenitor identities corresponding with the stages of cortical development in age-matched fetal brains.
2019-02-28 | GSE124174 | GEO
Project description:<p>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. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>
| phs001438 | dbGaP
Project description:The contribution of progenitor subtypes to generate the billions of neurons produced during human cortical neurogenesis is not well understood. We developed the Cortical ORganoid Lineage Tracing (COR-LT) system for human cortical organoids. Differential fluorescent reporter activation in distinct progenitor cells leads to permanent reporter expression, enabling the progenitor cell lineage of neurons to be determined. Surprisingly, nearly all excitatory neurons produced in cortical organoids were generated indirectly from intermediate progenitor cells, while astrocytes and inhibitory neurons were produced both directly and indirectly. Additionally, neurons of different progenitor lineages were transcriptionally distinct. Isogenic lines made from an autistic individual with and without a likely pathogenic variant in the CTNNB1 gene demonstrated that the variant substantially altered the proportion of neurons derived from specific progenitor cell lineages, as well as the lineage-specific transcriptional profiles of these neurons, suggesting a pathogenic mechanism for this mutation. These results suggest individual progenitor subtypes play unique roles in generating the diverse neurons of the human cerebral cortex.
2024-09-16 | GSE277159 | GEO
Project description:During development neural stem cells (NSCs) in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-06 | GSE254692 | GEO
Project description:During development neural stem cells (NSCs) in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-06 | GSE254691 | GEO
Project description:During development neural stem cells (NSCs) in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-06 | GSE254689 | GEO
Project description:During development neural stem cells (NSCs) in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-02 | GSE254690 | GEO
Project description:Cerebral organoids – three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells – have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.
2015-12-07 | GSE75140 | GEO
Project description:Neocortex expansion during evolution is linked to higher numbers of neurons thought to result from increased proliferative capacity and neurogenic potential of basal progenitors during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of both major basal progenitor types, intermediate basal progenitors and basal radial glia, whereas ablation of EPIREGULIN in human cortical organoids reduces basal progenitor proliferation. Here, we analyzed gene expression changes upon addition of EPIREGULIN to the mouse neocortex for 24 hours using hemisphere rotation culture. We performed fluorescent activated cell sorting to isolate radial glia (RG), intermediate progenitor (IP) cells and neurons (N) based on the nuclear markers Sox2 and Tbr2, and expression of GFP in neurons isolated from a Tubb3::GFP mouse reporter line.
2024-02-19 | GSE228007 | GEO
Project description:Cerebral organoids â three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells â have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).
2015-12-07 | E-GEOD-75140 | biostudies-arrayexpress