Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromatin regulator KDM6B is required for the establishment and maintenance of neural stem cells in mouse hippocampus

ABSTRACT: Neural stem cells in the mouse hippocampal dentate gyrus generate new neurons postnatally and throughout adult life. Here we show that the chromatin regulator KDM6B is required for both the establishment and maintenance of NSCs in the mouse DG. Conditional deletion of Kdm6b in embryonic DG precursors results in an adult hippocampus that is essentially devoid of NSCs, and hippocampal-dependent behaviors are defective. Kdm6b-deletion causes precocious neuronal differentiation, and the NSC population fails to become established in the postnatal DG. Using single cell RNA sequencing (scRNA-seq), we observed that Kdm6b-deletion disrupts the transcriptomic signature of NSC maintenance. Furthermore, deleting Kdm6b in adult DG NSCs induces early neuronal differentiation, and the NSC population is not properly maintained.

ORGANISM(S): Mus musculus

PROVIDER: GSE292677 | GEO | 2026/03/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE292677_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

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

Epigenetic maintenance of neural stem cell quiescence in the adult mouse hippocampus via Setd1a [RNA-Seq]

Project description:Quiescence, a hallmark of adult neural stem cells (NSCs), is required for maintaining the NSC pool to support life-long continuous neurogenesis in the adult dentate gyrus (DG). Whether epigenetic mechanisms can maintain NSC quiescence over long term in the adult brain is not well-understood. Here we showed that adult mice with haploinsufficiency of Setd1a, a schizophrenia risk gene encoding a histone H3K4 methyltransferase, exhibited substantially enlarged DG with increased number of dentate granule cells. Deletion of Setd1a specifically in quiescent NSCs in the adult DG promoted their activation and neurogenesis, which was countered by inhibition of histone demethylase LSD1. Mechanistically, RNA sequencing and CUT & RUN analyses of cultured quiescent adult NSCs revealed Setd1a deletion-induced transcriptional changes and Setd1a targets, among which down-regulation of Bhlhe40 promoted quiescent NSC activation in the adult DG. Together, our study revealed a Setd1a-dependent epigenetic mechanism that sustains NSC quiescence in the adult DG.

2024-03-31 | GSE250276 | GEO

Epigenetic maintenance of neural stem cell quiescence in the adult mouse hippocampus via Setd1a [Cut & Run]

2024-03-31 | GSE250275 | 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

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 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.

2011-12-31 | E-GEOD-21208 | biostudies-arrayexpress

Converged Epitranscriptomic Co-regulation of TGFβ Signaling Components Suppresses the Quiescence Transition of Early Postnatal Hippocampal Neural Stem Cells

Project description:Quiescence acquisition of proliferating neural stem cells (NSCs) is required to establish the adult NSC pool yet the underlying molecular mechanisms are not well-understood. Here we showed that conditional deletion of the m6A reader Ythdf2, which promotes mRNA decay, in proliferating NSCs in the early postnatal mouse hippocampus led to elevated quiescence acquisition with decreased neurogenesis. Multimodal profiling of m6A modification, YTHDF2 binding, and mRNA decay in hippocampal NSCs identified shared targets in multiple TGFβ signaling pathway components, including TGFβ ligands, maturation factors, receptors, transcription regulators, and signaling regulators. Functionally, Ythdf2 deletion led to TGFβ signaling activation in NSCs, suppression of which rescued elevated quiescence acquisition of proliferating hippocampal NSCs. Our study reveals the dynamic nature and critical roles of mRNA decay in establishing the quiescent adult hippocampal NSC pool and uncovers a novel mode of epitranscriptomic control via co-regulation of multiple components of the same signaling pathway.

2024-08-26 | GSE266096 | GEO

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

2011-12-31 | GSE21208 | GEO

Early Stem Cell Aging in the Mature Brain

Project description:Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initially compromise stem cell behavior represent early targets to enhance stem cell function later in life. Here, we pinpoint multiple factors that disrupt neural stem cell (NSC) behavior in the adult hippocampus. Clonal tracing showed that NSCs exhibit asynchronous depletion by identifying short-term (ST-NSC) and long-term NSCs (LT-NSCs). ST-NSC divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent LT-NSCs are maintained for months, but are pushed out of homeostasis by lengthening quiescence. Single cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of molecular aging in the mature brain and identified tyrosine-protein kinase Abl1 as an NSC pro-aging factor. Treatment with the Abl-inhibitor Imatinib increased NSC proliferation without impairing NSC maintenance in the middle-aged brain. Our study indicates that hippocampal NSCs are particularly vulnerable to cellular aging, yet NSC function can be partially restored.

2021-03-03 | GSE168031 | GEO

Ependyma-expressed CCN1 restricts the size of the neural stem cell pool in the adult ventricular-subventricular zone

Project description:Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular-subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ.

2020-02-19 | GSE137852 | GEO

Septo-dentate gyrus cholinergic circuits modulate function and morphogenesis of adult neural stem cells through granule cells in mice

Project description:Dentate gyrus (DG) is a critical structure for spatial memory and adult neurogenesis, and both processes are dynamically regulated by neural circuit activity. It remains unknown how neural circuits orchestrate the molecular landscape of the highly heterogeneous DG to regulate these distinct functions. Here we first report that activation of a cholinergic circuit from Diagonal Band of Broca to DG promotes both neural stem cell (NSC) activation and spatial memory. Furthermore, using single-nucleus RNA-sequencing of DG, we report broad transcriptomic changes across multiple types of mature and adult-born cells in response to cholinergic circuit activation. Notably, various neuronal populations exhibit abundant molecular changes that support synaptic functions crucial for spatial memory; while NSCs exhibit molecular changes that support their structural development and neurogenic proliferation. Interestingly, our electrophysiology and NicheNet analyses reveal granule cells, endothelial cells, and astrocytes as potential intermediaries for cholinergic activity-dependent NSC regulation. Our findings provide cell-type specific molecular mechanisms underlying cholinergic circuit activity-dependent regulation of distinct DG functions.

2024-09-04 | GSE202481 | 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