Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differential expression levels of Sox9 in early neocortical radial glial cells regulate the decision between stem cell maintenance and differentiation

ABSTRACT: Radial glial progenitor cells (RGCs) in the dorsal forebrain directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single cell RNA sequencing, we have studied gene expression patterns of two subtypes of RGCs that differ in their neurogenic behavior. One progenitor type rapidly produces postmitotic neurons, whereas the second progenitor remains relatively quiescence before generating neurons. We have identified candidate genes that are differentially expressed between these RGCs progenitor subtypes, including the transcription factor Sox9. Using in utero electroporation, we demonstrate that elevated Sox9 expression in progenitors prevents RGC division and leads to the generation of upper-layer cortical neurons from these progenitors at later ages. Our data thus reveal molecular differences between cortical progenitors with different neurogenic behavior and indicates that Sox9 is critical for the maintenance of RGCs to regulate the generation of upper layer neurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE179070 | GEO | 2021/06/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell RNA-sequencing of 75-day old human H1 and H9 embryonic stem cell-derived cerebral organoids

Project description:The scRNA-seq analysis of 75 day old human cerebral organoids grown at the air-liquid interface (ALI-COs) reveals six well-defined major clusters. Cell-type and maturity markers define a (1) distinct population of deep layer subcortical projection neurons, (2) upper layer intracortical (callosal) projection neurons and intermediate progenitors, (3) ventricular and subventricular zone radial glial cells, (4) more mature upper and deep layer neurons, (5) interneurons and (6) actively dividing cells with intermediate progenitor and radial glia markers. In addition, the gene expression profile of these clusters corresponds with their expected functional characteristics appropriate to their maturity. Altogether, our data reflect a full repertoire of cortical neuronal and progenitor identities corresponding with the stages of cortical development in age-matched fetal brains.

2019-02-28 | GSE124174 | GEO

Identification of the PRC1-interacting protein, L3mbtl3 as a novel gatekeeper of neocortical neurogenesis and proneural gene function [ATAC-seq]

Project description:The neocortex is comprised of six neuronal layers that are derived in an inside-out sequence. Neurog2, a proneural gene encoding a basic-helix-loop-helix transcription factor, is required and sufficient to specify the fate of only early-born, deep-layer neurons, despite being expressed throughout the cortical neurogenic period. To identify potential inhibitors of Neurog2 function, we used a TAP-tagging screen, identifying L3mbtl3, a histone methyl-lysine binding protein that interacts with Rnf2 in Polycomb Repressive Complex 1 (PRC1), as a novel Neurog2 interactor. We found that L3mbtl3 is co-expressed with Neurog2 and other PRC1 genes in cortical progenitors. In L3mbtl3 knock-out (KO) cortices, upper-layer neurons are generated in reduced numbers, and instead, the cortical progenitor pool is expanded. Transcriptomic analyses of L3mbtl3 KO cortices at early and mid neurogenesis revealed a striking upregulation of negative regulators of transcription, including Rest, a repressor of many neurogenic genes, and an associated downregulation of neuronal differentiation and maturation genes. Notably, transcriptomic changes occur in the absence of any changes to chromatin structure, suggesting that L3mbtl3 influences gene transcription directly and not via changes to the chromatin. Instead, L3mbtl3 represses Neurog2 transcriptional activity in vitro and blocks cortical progenitor cell maturation and neuronal migration in vivo by altering the expression of scaffold genes. L3mbtl3 is thus an essential negative regulator of cortical neurogenesis.

2021-07-06 | GSE179470 | GEO

Identification of the PRC1-interacting protein, L3mbtl3 as a novel gatekeeper of neocortical neurogenesis and proneural gene function

2021-07-06 | GSE179377 | GEO

BRG1 ChIP-Seq on E12.5 WT and LncBAR-KO (KO) neurospheres (passage 3)

Project description:Neocortical projection neurons of mammalian brains are largely direct daughters of intermediate progenitors (IP), which are progenies of radial glial cells (RG). The maintenance of the RG pool, production and expansion of IPs are essential for neocortical formation during development, as well as neocortical expansion during evolution. Here we characterized an epigenetic circuit that controls precise neurogenic programming of the neocortex. The circuit comprises a long non-coding RNA – LncBAR and the SWI/SNF (BAF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production of RGCs, but hampers neurogenic division and lengthens the cell-cycle durations of IPs during mid-later cortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage causes fewer adult neural stem cells at the subventricular zone, leading to compromised adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the SWI/SNF (BAF) chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with and the genomic locus of, and suppresses the expression of Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 re-expression in LncBAR-knockout neural precursors reversed compromised neurogenic divisions of IPCs. Together, we revealed a previously unidentified epigenetic machinery to control neurogenesis of neural precursors.

2021-10-27 | GSE169165 | GEO

RNA-Seq on E12.5 WT and LncBAR-KO (KO) neurospheres (passage 3)

2021-10-27 | GSE169164 | GEO

Extracellular matrix-inducing Sox9 orchestrates basal progenitor proliferation and gliogenesis in developing neocortex

Project description:Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. Examination of Sox9 expression reveals that Sox9 is expressed in BPs of developing ferret and human, but not mouse neocortex. Functional studies by conditional Sox9 expression in the mouse BP lineage demonstrate increased BP proliferation, reduced Tbr2 and induction of Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell non-autonomous stimulation of BP proliferation followed by increased production of upper-layer neurons. Collectively, our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic as well as gliogenic BP cell fate, suggesting that Sox9 acts a master regulator in the subventricular zone to promote neocortical expansion.

2020-03-27 | GSE134162 | GEO

Single cell analysis of iPSC-derived cortical organoids in biofunctionalized gelatin hydrogels

Project description:Human neural organoid models have become an important tool for studying neurobiology. In this work, we compared Matrigel to an N-cadherin peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. Specifically, we compare five materials: (1) Matrigel, (2) GelMA-Cad with high crosslinker (HC), (3) GelMA-Cad with low crosslinker (LC), (4) GelMA HC and (5) GelMA LC. We determined that both mechanical properties and peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad produce higher numbers of neurogenic and ciliated radial glia and upper-layer excitatory neurons—an important population for modeling neurodegenerative disease—compared to GelMA and Matrigel controls.

2024-02-28 | E-MTAB-13828 | biostudies-arrayexpress

Fezf2 overexpression in murine cortical progenitors in vivo

Project description:Corticospinal motor neurons (CSMN) are one specialized class of cortical excitatory neurons, which connect layer Vb of the cortex to the spinal cord. a master transcription factor –Forebrain expressed zinc finger 2 (Fezf2) – has been identified that is necessary for the fate specification of CSMN. Fezf2 alone can cell-autonomously instruct the acquisition of CSMN-specific features when expressed in diverse, permissive cellular contexts, in vivo. In order to understand the molecular logic underlying the acquisition of CSMN traits upon Fezf2 expression, we compared the in vivo gene expression of FACS-purified cortical progenitors that ectopically expressed Fezf2 to control progenitors. We used in utero electroporation to deliver Fezf2GFP or CtrlGFP expression vectors to neocortical progenitors at E14.5, when they primarily generate CPN of the upper layers. Overexpression of Fezf2 in these progenitors is sufficient to instruct a fate-switch resulting in the generation of CSMN and other subtypes of corticofugal projection neurons. Fezf2GFP- and CtrlGFP -electroporated progenitors were FACS-purified at 24 and 48 hours after surgery and acutely profiled by microarrays.

2014-07-06 | E-GEOD-56451 | biostudies-arrayexpress

Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity

Project description:Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.

2016-01-08 | E-GEOD-69790 | biostudies-arrayexpress

Upper cortical layer-driven network impairment in schizophrenia

Project description:Schizophrenia is one of the most wide-spread and complex mental disorders. To characterize the impact of schizophrenia, we performed single nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. Additionally, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most dramatic - in upper layer GABAergic neurons, including downregulation in energy metabolism and upregulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Finally, Visium spatial transcriptomics further corroborated upper layer neuron vulnerability in schizophrenia. Overall, our results point towards general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology. Study is available on bioRxiv (https://doi.org/10.1101/2020.11.17.386458) and in upcoming publication.

| EGAS00001006495 | EGA

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