Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE167955 | GEO | 2021/03/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.

Project description:Adult neurogenesis enables the life-long addition of functional neurons to the hippocampus and is regulated by both cell-intrinsic molecular programs and behavioral activity. De novo DNA methylation is crucial for embryonic brain development, but its role during adult hippocampal neurogenesis has remained unknown. Here, we show that de novo DNA methylation is critical for maturation and functional integration of adult-born neurons in the mouse hippocampus. Bisulfite sequencing revealed that de novo DNA methyltransferases target neuronal enhancers and gene bodies during adult hippocampal neural stem cell differentiation, to establish neuronal methylomes and facilitate transcriptional up-regulation of neuronal genes. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells did not affect proliferation or fate specification, but specifically impaired dendritic outgrowth and synaptogenesis of newborn neurons, thereby hampering their functional maturation. Consequently, abolishing de novo DNA methylation modulated activation patterns in the hippocampal circuitry and caused specific deficits in hippocampus-dependent learning and memory. Our results demonstrate that proper establishment of neuronal methylomes during adult neurogenesis is fundamental for hippocampal function.

| S-EPMC8441477 | biostudies-literature

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVitro_RRBS]

Project description:Dynamic DNA methylation controls gene-regulatory networks underlying cell fate specification. How DNA methylation patterns change during adult hippocampal neurogenesis and their relevance for the generation of new neurons from adult neural stem cells has, however, remained unknown. Here, we show that neurogenesis-associated de novo DNA methylation is critical for maturation and functional integration of adult-born hippocampal neurons. Cell stage-specific bisulfite sequencing revealed a pronounced gain of DNA methylation at neuronal enhancers, gene bodies and binding sites of pro-neuronal transcription factors during adult neurogenesis, which mostly correlated with transcriptional up-regulation of the associated loci. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells specifically impaired dendritic outgrowth and synaptogenesis of new neurons, resulting in impaired hippocampal excitability and specific deficits in hippocampus-dependent learning and memory. Our results highlight that, during adult neurogenesis, remodeling of neuronal methylomes is fundamental for proper hippocampal function.

2021-03-02 | GSE167954 | GEO

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVivo_RRBS]

2021-03-02 | GSE167953 | GEO

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [scRNA-seq]

2021-03-02 | GSE167952 | GEO

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.

Project description:De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis.

| PRJNA705660 | ENA

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVitro_RRBS]

Project description:De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVitro_RRBS]

| PRJNA705664 | ENA

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVivo_RRBS]

Project description:De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVivo_RRBS]

| PRJNA705665 | ENA

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [scRNA-seq]

Project description:De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [scRNA-seq]

| PRJNA705666 | ENA

Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.

Project description:Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.

| S-EPMC10997211 | biostudies-literature

Kruppel-like factor 9 is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis.

Project description:The dentate gyrus (DG) is modified throughout life by integration of new adult-born neurons. Similarities in neuronal maturation during DG development and adult hippocampal neurogenesis suggest that genetically encoded intrinsic regulatory mechanisms underlying these temporally distinct processes are conserved and reused. Here, we identify a novel transcriptional regulator of dentate granule neuron maturation, Krüppel-like factor 9 (Klf-9). We show that Klf-9 expression is induced by neuronal activity and as dentate granule neurons functionally integrate in the developing and adult DG. During development, dentate granule neurons lacking Klf-9 show delayed maturation as reflected by altered expression of early-phase markers, dendritic spine formation, and electrophysiological properties. Adult Klf-9-null mice exhibit normal stem cell proliferation and cell fate specification in the DG but show impaired differentiation of adult-born neurons and decreased neurogenesis-dependent synaptic plasticity. Behavioral analysis of Klf-9-null mice revealed a subtle increase in anxiety-like behavior and an impairment in contextual fear discrimination learning. Thus, Klf-9 is necessary for late-phase maturation of dentate granule neurons both in DG development and during adult hippocampal neurogenesis. Klf-9-dependent neuronal maturation may therefore represent a candidate regulatory mechanism underlying these temporally distinct processes.

| S-EPMC2753873 | biostudies-literature

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