Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of embryonic and adult neurogenesis by Ars2

ABSTRACT: Neural development is tightly controlled at multiple levels to orchestrate appropriate choices of cell fate and differentiation. While more attention has been paid to the roles of neural-restricted factors, broadly-expressed factors can have compelling impacts on tissue-specific development. Here, we describe in vivo genetic analysis of Ars2, which has mostly been studied as a general RNA processing factor in yeast and cultured cells. Ars2 protein exhibits a dynamic expression pattern during neural lineage progression, and conditional knockout analyses demonstrated that Ars2 is required for proliferation of embryonic neural stem cells (NSCs). In addition, Ars2 null neural stem cells can still transition into post-mitotic neurons, but fail to undergo terminal differentiation. Ars2 is similarly required for neurogenesis in the adult brain. We next generated Ars2 ChIP-seq data to broaden evidence for a distinct role for Ars2 as a transcriptional regulator in neural development. Notably, Ars2 preferentially occupies DNA enhancers in NSCs, and broadly colocalizes with the NSC regulator SOX2, but exhibits markedly reduced association with chromatin following differentiation. Finally, we demonstrate a continuous requirement for Ars2 during adult neurogenesis, since adult-specific deletion of Ars2 compromises hippocampal neurogenesis and results in specific behavioral defects. Together, we provide evidence for Ars2 as an essential neural regulator that interacts dynamically with DNA and controls neural lineage development.

ORGANISM(S): Mus musculus

PROVIDER: GSE134106 | GEO | 2020/01/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Developmental Cytoplasmic-to-Nuclear Translocation of RNA-Binding Protein HuR Is Required for Adult Neurogenesis

Project description:Although neurogenesis in the adult brain recapitulates processes that occur during embryonic development, adult neurogenesis exhibits distinct characteristics from its embryonic counterpart. However, the intrinsic mechanism underlying the differential regulation of neurogenesis between these two stages remains unclear. Herein, we show that the ablation of RNA-binding protein HuR in neural stem cells (NSCs) impairs adult, but not embryonic, neurogenesis. HuR is predominantly expressed in the cytoplasm of embryonic NSCs but translocates into the nucleus of adult NSCs. Transcriptomic analysis of HuR-deficient adult NSCs revealed that nuclear HuR primarily regulates alternative splicing of numerous premRNA transcripts, including focal adhesion kinase (FAK). HuR-deficient adult NSCs generate increased FAK mRNA isoforms with shorter 5’ UTRs, leading to enhanced FAK mRNA translation and hyperactivated FAK signaling, and inhibition of FAK ameliorates defective adult neurogenesis and impaired hippocampus-dependent learning in HuR-deficient mice. Taken together, these findings reveal novel mechanistic insights into the differential regulation of embryonic and adult neurogenesis through developmental cytoplasmic-to-nuclear translocation of HuR in NSCs.

2019-11-04 | GSE137323 | GEO

Post-transcriptional control of a stemness signature by RNA-binding 8 protein MEX3A regulates adult neurogenesis

Project description:Neural stem cells (NSCs) in the adult mammalian subependymal zone maintain a glial identity and the developmental potential to generate neurons during the lifetime. Production of neurons from these NSCs is not direct but follows an orderly pattern of cell progression which allows the gradual increase along the neurogenic lineage in the expression of pro-neural factors needed for neuronal specification. In this context, tightly regulated translation of existing transcriptional programs represents a potential mechanism to avoid the critical challenge posed by genes that encode proteins with conflicting functions, i.e. self-renew or differentiate. Here, we identify RNA-binding protein MEX3A as a post-transcriptional regulator of a set of stemness-associated transcripts at critical transitions in the subependymal neurogenic lineage. MEX3A binding to a set of quiescence-related RNAs in activated NSCs is needed for their return to quiescence, playing a role in the long-term maintenance of the NSC pool. Furthermore, it is required for the repression of the same program at the onset of neuronal differentiation. Our data indicate that MEX3A is a pivotal regulator of adult mammalian neurogenesis acting as a translational remodeller.

2023-01-08 | PXD038983 | Pride

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

Dual and separable roles for Ezh2 in neurogenic astroglia

Project description:The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes that specify non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis. Examination of histone modifications (H3K27me3 and H3K4me3) in subventricular zone neural stem cells

2014-05-02 | E-GEOD-56394 | biostudies-arrayexpress

Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) controls hippocampal neural stem cell conversion into progenitor cells

Project description:Neural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. However, this process declines with age and this decline correlates with defects in cognitive function and mood. Molecular mechanisms that activate quiescent NSCs to generate progenitor cells in vivo remain poorly understood. Here we show that adult hippocampal NSCs express VEGFR3, a key regulator of vascular and neural development, and are activated by the VEGFR3 ligand VEGF-C to enter the cell cycle and convert into progenitor cells. Conditional deletion of Vegfr3 in NSCs leads to a decline in hippocampal neurogenesis. Functionally, this is associated with increased anxiety behavior and compromised NSC activation in response to VEGF-C and physical activity. These findings establish VEGFR3 expression as a hallmark of adult mouse NSCs and demonstrate a specific requirement for VEGF-C/VEGFR signaling in NSC activation. Enhancing VEGFR3 signaling by VEGF-C may improve neurogenesis and mood during aging.

2014-03-06 | GSE55621 | GEO

mRNA-Seq and microRNA-Seq whole-transcriptome analysis of rhesus monkey ESC neural differentiation revealed the potential rosette neural stem cell regulators

Project description:Rosette neural stem cells (R-NSCs) represent early stage of neural development and possess full neural differentiation and regionalization capacities. R-NSCs are considered as stem cells of neural lineage and have important implications in study of neurogenesis and cell replacement therapy. However, the molecules regulating their functional properties remain largely unknown. Rhesus monkey is ideal model to study human neural degenerative diseases and plays intermediate translational roles as therapeutic strategies evolve from rodent systems to human clinical applications. In this study, we derived R-NSCs from rhesus monkey embryonic stem cells (rESCs) and systematically investigated the unique expressions of mRNAs, microRNAs, and signaling pathways by genome-wide comparison of the mRNA and microRNA profilings of ESCs, R-NSCs at early (R-NSCP1) and late passages (R-NSCP6) and neural progenitor cells (NPCs). Apart from the R-NSCP1 specific protein-coding genes and microRNAs, we identified several pathways including Hedgehog and Wnt highly activated in R-NSCP1. The possible regulatory interactions among the microRNAs, protein-coding genes and signaling pathways were proposed. Besides, many genes with alternative splicing switch were identified at R-NSCP1. These data provided valuable resource to understand the regulation of early neurogenesis and to better manipulate the R-NSCs for cell replacement therapy. mRNA and miRNA profiles for four stages in rhesus embryonic stem cell neural differentiation, eight samples in all

2014-07-03 | E-GEOD-53260 | biostudies-arrayexpress

SAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize Nfib mRNA

Project description:Neural stem cell regulation is essential for the formation of the central nervous system and homeostatic neurogenesis in the adult mammalian brain. The RNAseIII Drosha, a key component of the miRNA microprocessor, plays a central role in regulating NSC maintenance partially through a miRNA-independent mechanism. Drosha controls mRNA expression levels by targeting and cleaving evolutionary conserved stem-loop hairpins located in the mRNAs of stem cell-related transcription factors. However, it is unknown how the Drosha-mediated endonucleolytic cleavage of mRNA is regulated. Here, we identify novel Drosha and NFIB interactors in hippocampal NSCs by in vitro pull-down assays followed by Mass Spectrometry. We unravel the RNA binding proteins implicated in Drosha-mediated regulation of neurogenesis and we find Scaffold Attachment Factor B1 to play a novel and essential role in NFIB mRNA regulation during neural stem cell differentiation.

2024-06-03 | PXD017677 | Pride

Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects impairing adult neurogenesis.

Project description:Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs regulate stem cell self-renewal and differentiation. We used comprehensive and untargeted single-cell RNA profiling to generate a molecular cell atlas of the largest germinal region of the adult mouse brain, the subventricular zone (SVZ). We characterized > 20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we applied our single-cell approach to document decreased numbers of NSCs, reduced proliferation activity of progenitors, and perturbations in Wnt and BMP signaling pathways in mice lacking LRP2, an endocytic receptor required for SVZ maintenance. Our data provide a valuable resource to study adult neurogenesis and a proof-of-principle for the power of single-cell RNA-sequencing to elucidate neural cell type-specific alterations in loss-of-function models.

2018-11-26 | GSE111527 | GEO

Dual and separable roles for Ezh2 in neurogenic astroglia

2014-05-02 | GSE56394 | GEO

Mex3a RIP-seq

Project description:Neural stem cells (NSCs) in the adult mammalian subependymal zone maintain a glial identity and the developmental potential to generate neurons during the lifetime. Production of neurons from these NSCs is not direct but follows an orderly pattern of cell progression which allows the gradual increase in pro-neural factors needed for neuronal fate. Although little is known about how stemness is molecularly balanced with the acquisition of the cell competence for neuronal differentiation along the lineage, regulated translation of existing transcripts is a potential mechanism to avoid the critical challenge posed by genes that encode proteins with conflicting functions, i.e. self-renew or differentiate. Here, we identify MEX3A as a post-transcriptional regulator of a set of stemness-associated transcripts at critical transitions in the subependymal neurogenic lineage. MEX3A regulates a quiescence-related RNA signature in activated NSCs that is needed for the return to quiescence, playing a role in the long-term maintenance of the NSC pool. Furthermore, it is required for the repression of the same program at the onset of neuronal differentiation. Our data indicate that MEX3A acts via a number of downstream targets to function as a pivotal regulator of adult mammalian neurogenesis.

2022-12-19 | GSE184404 | 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