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Generation of human cerebral organoids with a structured outer subventricular zone

ABSTRACT: Generation of human cerebral organoids with a structured outer subventricular zone

PROVIDER: PRJNA930689 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23318400.fastq.gz	Fastqsanger.gz
	SRR23318401.fastq.gz	Fastqsanger.gz
	SRR23318402.fastq.gz	Fastqsanger.gz
	SRR23318403.fastq.gz	Fastqsanger.gz
	SRR23318404.fastq.gz	Fastqsanger.gz

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Generation of human cerebral organoids with a structured outer subventricular zone

Project description:Outer radial glia (oRG) emerged during mammalian evolution as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. The in vitro generation of oRG is essential to model and investigate the underlying mechanisms of human neocortex development and expansion. By activating the STAT3 pathway using LIF, which is not produced in guided cortical organoids, we developed a cerebral organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The structured oSVZ is composed of progenitor cells expressing specific oRG markers such as GFAP, LIFR, HOPX and closely matching human oRG in vivo. In this microenvironment, cortical neurons showed faster maturation with enhanced metabolic and functional activity. Incorporation of hPSC-derived brain vascular LIF-producing pericytes in cerebral organoids mimicked the effects of LIF treatment. These data indicate that the cellular complexity of the cortical microenvironment, including cell types of the brain vasculature, favors the appearance of oRG and provides a platform to routinely study oRG in hPSC-derived brain organoids.

2024-04-15 | GSE224346 | GEO

Generation of human cerebral organoids with a structured outer subventricular zone.

Project description:Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The oSVZ comprises progenitor cells expressing specific oRG markers such as GFAP, LIFR, and HOPX, closely matching human fetal oRG. Finally, incorporating neural crest-derived LIF-producing cortical pericytes into cortical organoids recapitulates the effects of LIF treatment. These data indicate that increasing the cellular complexity of the organoid microenvironment promotes the emergence of oRG and supports a platform to study oRG in hPSC-derived brain organoids routinely.

| S-EPMC11322983 | biostudies-literature

A restricted period for formation of Outer Subventricular Zone defined by Cdh1 and Trnp1 levels

Project description:The Outer Subventricular Zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species like human and ferret where it contains abundant basal Radial Glia Cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident down-regulation of Cdh1 and Trnp1, and their up-regulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease Samples were analyzed with 3 replicates of each of them (except E34SVZ that has 2 replicantes). Comparisons were done taking different reference sample depending on the comparison.

2016-06-01 | E-GEOD-63203 | biostudies-arrayexpress

A restricted period for formation of Outer Subventricular Zone defined by Cdh1 and Trnp1 levels

2016-06-01 | GSE63203 | GEO

subventricular zone progenitors healthy vs. Experimental Autoimmune Encephalomyelitis mice

Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors.

2013-09-09 | GSE47486 | GEO

Single cell expression profiling of murine subventricular zone in adult brain three days after focal celebral ischemia

Project description:Ischemic stroke is a serious medical condition that leads to the onset of neurological symptoms such as loss of motor and cognitive functions. Focal cerebral ischemia (FCI) occurs due to the interrupted blood supply to the site of injury, resulting in the demise of brain cells. The subventricular zone (SVZ) is a source of stem and progenitor cells (NS/PCs), which proliferate and differentiate in multiple cell types in order to substitute the injured tissue. We isolated cells from the SVZ and the adjacent striatum three days after middle cerebral artery occlusion (MCAO) in order to map cellular changes and NS/PCs plasticity in adult brain upon injury. Expression profiling of the isolated tissue at the single cell level enables the identification of cell population subtypes in the region and their characteristic gene expression.

2021-01-01 | E-MTAB-9935 | biostudies-arrayexpress

Identity and Nature of Neural Stem Cells in the Adult Human Subventricular Zone

Project description:The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early-lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

2023-12-27 | GSE248995 | GEO

High-resolution transcriptome analysis of mouse subventricular zone reveals features of stem cell lineage, anatomy, and aging

Project description:Single cell RNA sequencing of mouse subventricular zone (SVZ) harboring a CGD1 transgene expressing GFP.

2017-11-22 | GSE107220 | GEO

Single-cell gene expression of the subventricular zone (SVZ) neurogenic niche after partial reprogramming

Project description:Partial reprogramming has the potential to reverse age-related decline in some tissues. Its impact on the cell types within the aging brain, particularly the subventricular zone neurogenic niche, is unknown.

2024-02-04 | GSE224438 | GEO

Transcriptome Response and Spatial Pattern of Gene Expression in the Primate Subventricular Zone Neurogenic Niche After Cerebral Ischemia

Project description:The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal- and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult.

2019-08-23 | GSE136036 | GEO

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