Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis

ABSTRACT: Neural stem cells (NSCs) generate new neurons throughout life in two distinct areas of the mammalian brain: the subventricular zone (SVZ) lining the lateral ventricles and the hippocampal dentate gyrus (DG). How gene expression signatures differ among NSCs and immature neurons within and between these adult neurogenic regions is unknown. We isolated NSCs and their progeny using transgenic mice expressing GFP under the control of the Sox2 promoter (labeling NSCs) and transgenic mice expressing DsRed under the control of the doublecortin (Dcx) promoter (labeling immature neurons). Comparison of the transcriptomes of SOX2+ cells derived from both neurogenic areas revealed that NSCs are highly similar but that functionally significant differences in gene expression exist: IGF2, which is expressed only in SOX2+ cells in the DG but not in the SVZ, is required for proliferation of DG-derived but not SVZ-derived NSCs. Gene expression profiles strongly diverged in immature neurons, and we provide evidence that ephrinB3, which was up-regulated only in the DG but not in the SVZ during neuronal differentiation, regulates the survival of newborn granule cells. Thus, the data provided here show that stem cell populations in the adult DG and SVZ are similar but have unique properties that manifest themselves later during neural differentiation, resulting in distinct neuronal populations Hippocampi and SVZ from 6 week old DCX-DsRed and Sox2-GFP Reporter mice were dissected and cell sorted using FACS. cDNA were generated and analysed using Agilent Platform.

ORGANISM(S): Mus musculus

SUBMITTER: Oliver Bracko

PROVIDER: E-GEOD-21208 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis

Project description:Neural stem cells (NSCs) generate new neurons throughout life in two distinct areas of the mammalian brain: the subventricular zone (SVZ) lining the lateral ventricles and the hippocampal dentate gyrus (DG). How gene expression signatures differ among NSCs and immature neurons within and between these adult neurogenic regions is unknown. We isolated NSCs and their progeny using transgenic mice expressing GFP under the control of the Sox2 promoter (labeling NSCs) and transgenic mice expressing DsRed under the control of the doublecortin (Dcx) promoter (labeling immature neurons). Comparison of the transcriptomes of SOX2+ cells derived from both neurogenic areas revealed that NSCs are highly similar but that functionally significant differences in gene expression exist: IGF2, which is expressed only in SOX2+ cells in the DG but not in the SVZ, is required for proliferation of DG-derived but not SVZ-derived NSCs. Gene expression profiles strongly diverged in immature neurons, and we provide evidence that ephrinB3, which was up-regulated only in the DG but not in the SVZ during neuronal differentiation, regulates the survival of newborn granule cells. Thus, the data provided here show that stem cell populations in the adult DG and SVZ are similar but have unique properties that manifest themselves later during neural differentiation, resulting in distinct neuronal populations

2011-12-31 | GSE21208 | GEO

Integrative Single-Cell Transcriptomics Reveals Molecular Networks Defining Neuronal Maturation during Neurogenesis

Project description:Neurogenesis in the adult hippocampus contributes to information processing critical for cognition, adaptation, learning and memory, and is implicated in numerous neurological disorders. New neurons are continuously produced from neural stem cells via a well-controlled developmental process. The immature neuron stage defined by doublecortin (DCX) expression is the most sensitive to regulation by extrinsic factors. However, little is known about the dynamic biology within this critical interval that drives maturation and confers susceptibility to regulating signals. This study aims to test the hypothesis that DCX-expressing immature neurons in adult mouse hippocampus progress through developmental stages via activity of specific transcriptional networks. Using single-cell RNA-seq combined with a novel integrative bioinformatics approach, we discovered that individual immature neuron can be classified into distinct developmental subgroups based on characteristic gene expression profiles and subgroup-specific markers. Comparisons between immature and more mature subgroups revealed novel pathways involved in neuronal maturation. Genes enriched in more immature cells shared significant overlap with genes implicated in neurodegenerative diseases, while genes positively associated with neuronal maturation were enriched for autism-related gene sets. Our study thus discovers molecular signatures of individual adult-born immature neurons and unveils potential novel targets for therapeutic approaches to treat neurodevelopmental and neurological diseases. mRNA sequencing and expression estimation in 64 individual DCX-dsRed+ cells isolated from transgenic DCX-dsRed mice by FACS sorting

2016-02-29 | E-GEOD-75901 | biostudies-arrayexpress

Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone in vitro

Project description:Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, which laid a foundation for studying the activation mechanism of qNSCs.

2024-06-26 | GSE267115 | GEO

FACS Sequencing Analysis of DCX+ cells in the DG of Wild Type and Fmr1-/y; Dcx-DsRed mice

Project description:Purpose: The goals of this study are to investigate the molecular mechanism underlying FMRP-regulated maturation of newborn neurons Methods: DG tissue were isolated from 6-7 weeks old Fmr1-/y; Dcx-DsRed mice and their WT littermates. All cell populations were isolated into single cells using a Becton Dickinson FACS Aria II contained in a Biosafety Carbinet using 20 psi pressure and 100-μm nozzle aperture. 10,000 total alive or Dcx-DsRed+ alive Cells were collected directly in Trizol. Total RNA from the sorted cell was isolated using the Direct-zol™ RNA MiniPrep Kit. Strand-specific, poly(A) selected cDNA libraries were generated using Nugen Ovation® Ultralow Library Systems (Illumina) according to the manufacturer’s protocol. Cluster generation and high-throughput sequencing were performed on a HiSeq 2500 (Illumina), using the paired-end 100 bp protocol. Reads were aligned to the mouse genome GRCm38 with annotation from Gencode. Results: RNA isolated from DsRed+ cells were subjected to next generation sequencing and 519 differentially expressed (DE) genes were identified that showed significant changes (FDR-adjusted P < 0.05) between Fmr1 KO and WT cells.

2019-01-31 | GSE117111 | GEO

Single cell RNA sequencing of aging neural progenitors reveals loss of excitatory neuron potential and a population with transcriptional immune response (scRNA-Seq)

Project description:In the adult murine brain, neural stem cells (NSCs) reside in two main niches, the dentate gyrus (DG), and the subventricular zone (SVZ). In the DG, NSCs give rise to intermediate progenitors that differentiate into excitatory neurons, while progenitors in the SVZ migrate to the olfactory bulb (OB) where they mainly differentiate into inhibitory interneurons. Neurogenesis, the production of new neurons, persists throughout life but decrease dramatically during aging, concomitantly with increased inflammation. Many cell types, including microglia, undergo dramatic transcriptional changes but few such changes have been detected in neural progenitors. Furthermore, transcriptional profiles in progenitors from different neurogenic regions have not been compared at single cell level, and little is known about how they are affected by age-related inflammation. We have generated a single cell RNA sequencing dataset enriched for intermediate progenitors, which revealed that most aged neural progenitors only acquire minor transcriptional changes. However, progenitors set to become excitatory neurons decrease faster than others. In addition, a population in the aged SVZ, not detected in the OB, acquired major transcriptional activation related to immune responses. This suggests that differences in age related neurogenic decline between regions is not due to tissue differences but rather cell type specific intrinsic transcriptional programs, and that subset of neuroblasts in the SVZ react strongly to age related inflammatory cues.

2024-07-29 | GSE261458 | GEO

Single cell RNA sequencing of aging neural progenitors reveals loss of excitatory neuron potential and a population with transcriptional immune response (RNA-Seq)

2024-07-29 | GSE261457 | GEO

FACS Sequencing Analysis of DCX+ cells in the DG of Wild Type and Fmr1-/y Dcx-DsRed mice

Project description:FACS Sequencing Analysis of DCX+ cells in the DG of Wild Type and Fmr1-/y Dcx-DsRed mice

| PRJNA481059 | ENA

RNA-sequencing gene expression data from FACS-purified Ventricular-Subventricular Zone (V-SVZ) and cortical cells from hGFAP::GFP mice.

Project description:Quiescent neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) undergo activation and divide to generate neurons and glia. Here we show that Platelet-derived Growth Factor Receptor beta (PDGFRβ) is expressed by quiescent and early activated adult V-SVZ NSCs, and maintains their quiescence. We further showed that selective deletion of PDGFRβ in adult V-SVZ NSCs leads to activation of quiescent NSCs. We performed RNA-seq on FACS-sorted V-SVZ quiescent, early activated and late activated NSCs, as well as cortical cells from adult 2-4 month old mice.

2021-05-01 | GSE118009 | GEO

Intracrine Vascular Endothelial Growth Factor Maintains Hippocampal Neural Stem Cell Quiescence

Project description:In the dentate gyrus (DG) of the adult mouse hippocampus, neural stem cells (NSCs) balance self-renewal and differentiation to produce neurons that support hippocampal function. Vascular endothelial growth factor (VEGF) is a well-known supporting factor for adult neurogenesis, but conflicting studies have left it uncertain how VEGF signals to NSCs. Here, we identified a VEGF-VEGFR2 intracrine signaling mechanism within adult DG NSCs that prevents their exhaustion. We show both in vitro and in vivo that NSC-VEGF loss caused cell-autonomous exhaustion of adult DG NSCs. In contrast, extracellular VEGF was neither necessary nor sufficient to maintain NSC quiescence or to stimulate VEGFR2 signaling, most likely due to sheddase-mediated cleavage of extracellular VEGFR2 ligand binding domains. Our findings support an exclusively intracellular mechanism for VEGF signaling in adult DG NSCs, thereby providing resolution to previously conflicting studies and suggesting cellular source can dictate the functional impact of soluble ligands in DG NSCs.

2024-04-16 | GSE220871 | GEO

Histone lysine demethylase JMJD3/KDM6B is required for the establishment of adult hippocampal neurogenesis

Project description:Mutations in the JMJD3 (KDM6B) chromatin regulator are causally associated with autism spectrum disorder and syndromic intellectual disability, but the neurodevelopmental roles of this histone 3 lysine 27 (H3K27) demethylase are poorly understood. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) generate new granule neurons throughout life, and deficits in DG neurogenesis are associated with cognitive and behavioral problems. Here we show that Jmjd3 is required for the establishment of adult neurogenesis in the mouse DG. Conditional deletion of Jmjd3 in embryonic DG precursors results in an adult hippocampus that is essentially devoid of NSCs. While early postnatal mice with Jmjd3-deletion have near normal numbers of DG NSCs, at later stages, Jmjd3-deleted NSCs fail to propagate normally. In addition to the loss of NSCs during postnatal development, neurogenesis from Jmjd3-deleted NSCs is impaired, corresponding to defective neurogenic gene expression. Without Jmjd3, NeuroD2 and Bcl11b(Ctip2) are not properly expressed and exhibit increased levels of H3K27me3, underscoring the role of Jmjd3 in the regulation of transcription for neuronal differentiation. Thus, these data indicate that Jmjd3 plays dual roles in postnatal DG neurogenesis, being critical for the establishment of the NSC pool as well as the differentiation of young DG granule neurons. More broadly, our results suggest a neurodevelopmental link between JMJD3 mutations and hippocampal dysfunction, providing new insights into how mutations in chromatin regulators may contribute to learning disorders.

2021-04-01 | GSE73706 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data