Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mitochondria Metabolism Sets the Species-Specific Tempo of Neuronal Development

ABSTRACT: Neuronal development in the human cerebral cortex is considerably prolonged compared to that of other mammals. We explored whether mitochondria influence the species-specific timing of cortical neuron maturation. By comparing human and mouse cortical neuronal maturation at high temporal and cell resolution, we found a slower mitochondria development in human cortical neurons compared with that in the mouse, together with lower mitochondria metabolic activity, particularly that of oxidative phosphorylation. Stimulation of mitochondria metabolism in human neurons resulted in accelerated development in vitro and in vivo, leading to maturation of cells weeks ahead of time, whereas its inhibition in mouse neurons led to decreased rates of maturation. Mitochondria are thus important regulators of the pace of neuronal development underlying human-specific brain neoteny.

ORGANISM(S): Homo sapiens

PROVIDER: GSE219253 | GEO | 2023/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A hominoid-specific signaling axis setting the tempo of synaptic maturation

Project description:Compared to that of other mammals, human cortical neurons exhibit higher dendritic complexity and synaptic density, and the maturation process is much protracted. However, the molecular mechanism governing these specific features is unclear. Here, we report that the hominoid-specific gene TBC1D3, a core duplicon in the human genome, promotes dendritic arborization and maintains the slow pace of synaptogenesis. Furthermore, to gain insights into the mechanism by which the TBC1D3-MICAL1-ATRX complex determines the slow pace of spinogenesis, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) experiment using an ATRX antibody targeting the C-terminal region in cultured mouse cortical neurons.

2024-03-31 | GSE246002 | GEO

A hominoid-specific signaling axis setting the tempo of synaptic maturation II

2024-04-10 | GSE263014 | GEO

Fully defined NGN2 neuron protocol reveals diverse signatures of neuronal maturation

Project description:NGN2-driven iPSC-to-neuron conversion is a popular method for human neurological disease modeling. In this study, we report a fully standardized approach for generating functional excitatory cortical neurons. This method utilizes clonal, targeted-engineered iPSC lines and employs fully defined reagents. We demonstrate that our protocol generates consistent excitatory cortical neurons at scale. Comprehensive temporal omics, electrophysiological, and morphological profilings indicate the continued progression of neuronal maturation for at least 150 days. Deep quantitative characterizations through transcriptomic, imaging, and functional assays reveal coordinated actions of multiple pathways driving neuronal maturation. The neurons express the majority of the key risk genes in Alzheimer's disease, Parkinson's disease, and autism, demonstrating the relevance of our protocol in modeling human neurological disorders. This well-defined method, profiling data, and functional characterization provide a solid and reliable framework for developing human in vitro neuronal models for disease modeling.

2023-10-18 | MSV000093150 | MassIVE

Transcription profiling of mouse wild type vs Dnmt1 hypomethylated forebrain

Project description:DNA methylation is a major epigenetic factor regulating genome reprogramming, cell differentiation, developmental gene expression. To understand the role DNA methylation in CNS neurons, we generated conditional Dnmt1 mutant mice that possess ~90% hypomethylated cortical and hippocampal cells in the dorsal forebrain from E13.5 on. The mutant mice were viable with a normal lifespan, but displayed severe neuronal cell death between E14.5 to 3-weeks postnatally. Accompanied with the striking cortical and hippocampal degeneration, adult mutant mice exhibited neurobehavioral defects in learning and memory in adulthood. Unexpectedly, a fraction of Dnmt1-/- cortical neurons survived through postnatal development, so that the residual cortex in mutant mice contained 20-30% of hypomethylated neurons throughout the life. Hypomethylated excitatory neurons exhibited multiple defects in postnatal maturation including abnormal dendritic arborization and impaired neuronal excitability. The mutant phenotypes are coupled with deregulation of those genes involved in neuronal layer-specification, cell death, and the function of ion channels. Our results suggest that DNA methylation, through its role in modulating neuronal gene expression, plays multiple roles in regulating cell survival, neuronal migration and maturation in the CNS. Experiment Overall Design: We compared gene expression patterns in Wildtype and DNA methylation deficient (Emx1-cre; Dnmt1 mutant) mouse dorsal cortex. We performed 3 replicates using different each individual mouse strain. The Sample GSM350992 table is the average log ratio for the 3 replicatesArrays were performed in triplicate.

2009-12-18 | E-GEOD-14216 | biostudies-arrayexpress

Mitochondria Metabolism Sets the Species-Specific Tempo of Neuronal Development

Project description:Mitochondria Metabolism Sets the Species-Specific Tempo of Neuronal Development

| PRJNA907814 | ENA

Mitochondria Metabolism Sets the Species-Specific Tempo of Neuronal Development

Project description:Mitochondria dynamics and metabolism drive the species-specific developmental timing of cortical neurons.

| PRJEB58006 | ENA

Identification of response genes upon neuronal activation in mouse cortical neurons

Project description:We search for developmental changes specific to humans by examining gene expression profiles in the human, chimpanzee and rhesus macaque prefrontal and cerebellar cortex. In both brain regions, developmental patterns were more evolved in humans than in chimpanzees. The major human specific genes in prefrontal cortex was enriched in neuronal functions and regulated by several transcription factors, which were previously implicated in regulation of neuronal functions. To confirm neuronal function of the human prefrontal cortex specific genes, we identifed response genes upon neuronal activation in mouse cortical neurons. Our results show that human specific genes are enriched in the response genes upon neuronal activation, implying the function of human prefrontal cortex specific genes in synaptic development. The cortical neurons from E15 mouse were isolated and cultured. We then exposed neurons to bicuculline (Bic), or potassium chloride (KCl), or without treatment. The cultured neurons under each group were hybridized to Agilent whole mouse genome oligo microarray (4x44k).

2012-02-02 | E-GEOD-29139 | biostudies-arrayexpress

RNA-seq and ChIP-seq for human-specific regulation of neural maturation identified by cross-primate transcriptomics

Project description:Brain development is exceptionally delayed in humans compared to nonhuman primates (NHPs), a finding often termed neoteny. Signatures of neoteny, including a protracted proliferation of apical and basal progenitors as well as a delay in physiological activity of mature neurons, have been revealed in part through the use of induced pluripotent stem cell (iPSC) modeling of primate neurogenesis. IPSC modeling is particularly useful when examining the molecular drivers of a cellular phenotype such as gene transcription. It has long been proposed that phenotypic differences between closely related species may be driven, in part, by divergent transcriptional regulation rather than novel protein-coding sequence, however, how these regulatory mechanisms play a role in the protracted maturation process in human neurons remains largely unknown. Here we show that the transcription factor GATA3 directly regulates the rate of physiological maturity in human neurons. We modeled neurogenesis across 5 primate species consisting of 4 genera and 2 families and assessed the differences in transcriptional dynamics. We discovered that GATA3, a pioneer transcription factor, exhibited a unique up-regulation during human neurogenesis and was highly correlated with species-specific transcription. Strikingly, we also found that down-regulating GATA3 generated a gain-of-function, speeding up the rate of physiological maturity in human neurons. These findings indicate that the rate of physiological maturity in human neurons can be directly controlled by modulating a single, conserved transcription factor, providing evidence for the divergence of gene regulation as a major contributor to human neoteny.

2020-09-20 | GSE120271 | GEO

HtrA1-dependent proteolysis of TGF-M-NM-2 controls both neuronal maturation and developmental survival

Project description:Transforming growth factor-M-NM-2 (TGF-M-NM-2) signalling controls a number of cerebral functions and dysfunctions including synaptogenesis, amyloid-M-NM-2 accumulation, apoptosis and excitotoxicity. Using cultured cortical neurons prepared from either wild type or transgenic mice over-expressing a TGF-M-NM-2 responsive luciferase reporter gene (SBE-Luc), we demonstrated a progressive loss of TGF-M-NM-2 signalling during neuronal maturation and survival. Moreover, we showed that neurons exhibit increasing amounts of the serine protease HtrA1 (high temperature responsive antigen 1) and corresponding cleavage products during both in vitro neuronal maturation and brain development. In parallel of its ability to promote degradation of TGF-M-NM-21, we demonstrated that blockage of the proteolytic activity of HtrA1 leads to a restoration of TGF-M-NM-2 signalling, subsequent overexpression of the serpin type -1 plasminogen activator inhibitor (PAI-1) and neuronal death. Altogether, we propose that the balance between HtrA1 and TGF-M-NM-2 could be one of the critical events controlling both neuronal maturation and developmental survival. Keywords: HtrA1 / neuronal survival / PAI-1 / TGF-M-NM-2 signalling / tPA Total RNA were extracted from 3 cultures of 2 DIV Human neurons. For each stage, equal amounts of each RNA were pooled and 5M-BM-5g were reverse-transcribed, labelled and hybridized on pangenomic microarrays. Each pool was hybridized in duplicate dye-swap independent experiments.

2008-04-15 | E-GEOD-11162 | biostudies-arrayexpress

WT vs Hypomethylated Forebrain Gene Expression

2009-12-12 | GSE14216 | GEO