Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fixed single-cell transcriptomic characterization of human radial glial diversity

ABSTRACT: The human neocortex is created from diverse progenitors that are intermixed with multiple cell types in the prenatal germinal zones. These progenitors have been difficult to profile with unbiased transcriptomics since progenitors-particularly radial glia (RG)-are rare cell types, defined by a combination of intracellular markers, position and morphology. To circumvent these problems, we developed a method called FRSCR for transcriptome profiling of individual fixed, stained, and sorted cells. After validation of FRSCR with human embryonic stem cells, we profiled primary human RG that constitute only 1% of the mid-gestation cortex. These data showed that RG could be classified into ventricle zone-enriched RG (vRG) that expressed ANXA1 and CRYAB, and outer subventricular zone-localized RG (oRG) that expressed HOPX. Our study identified the first markers and molecular profiles of vRG and oRG cells, and provides an essential step for understanding molecular networks that control the development and lineage of human neocortical progenitors. Furthermore, FRSCR allows targeted single-cell transcriptomic profiling of many tissues that currently lack live-cell markers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71858 | GEO | 2015/10/02

SECONDARY ACCESSION(S): PRJNA292324

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Fixed Single Cell Study (Radial Glia Cells)

Project description:The human neocortex is created from diverse intermixed progenitors in the prenatal germinal zones. These progenitors have been difficult to characterize since progenitors - particularly radial glia (RG) - are rare, and are defined by a combination of intracellular markers, position and morphology. To circumvent these problems we developed a method called FRISCR (Fixed and Recovered Intact Single Cell RNA) for transcriptome profiling of individual fixed, stained and sorted cells. We developed and validated FRISCR on human embryonic stem cells. We then profiled primary human RG (96 - 132 days post conception) that constitute only 1% of the mid-gestation cortex. These RG could be classified into ventricular zone-enriched RG (vRG) that express ANXA1 and CRYAB, and outer subventricular zone-localized RG (oRG) that express HOPX. Our study identifies the first markers and molecular profiles of vRG and oRG cells, and provides an essential step for understanding molecular networks driving the lineage of human neocortical progenitors. Reprinted from Thomsen et. al. Nature Methods (2015), with permission from Nature Publishing. Human embryonic stem cell data may be obtained through NCBI's GEO database, using accession number <a href="http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71858">GSE71858</a>. Raw data from one human sample that was not consented to be released to dbGaP may be obtained directly from the authors of Thomsen et. al., 2015.

| phs001016 | dbGaP

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed an integrated clinicogenomic analysis of 36 AB-like tumors. Lesions with MN1-BEND2 fusions demonstrated decreased promoter methylation and increased expression of IGF2-H19 and DLK1-DIO3 imprinted region genes. They also relatively overexpressed genes highly expressed during fetal brain development prior to 25 post-conception weeks (pcw), including genes enriched in ventricular zone radial glia (vRG), and generally presented in young children. Other tumors highly expressed MAP kinase pathway, PI3K pathway and X-inactivation escape genes. These and a third group of tumors tended to occur in young adults and showed enriched expression of outer radial glia (oRG) and truncated radial glia (tRG) genes, and genes highly expressed after 25 pcw. Many of the latter are involved in axonal migration or synaptic plasticity and are implicated in autism, schizophrenia and other cognitive disorders. Findings suggest that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors during fetal and later brain development: early ependymal tumors with MN1-BEND2 fusions (EET-MN1) from vRG-derived progenitor cells, and MAPK/PI3K and classic astroblastomas from oRG- and tRG-derived progenitors, respectively. Lastly, we found that like EET-MN1, immature ependymal cells express IGF2 and may represent an important source of this growth factor in the fetal lateral ventricular zone neural stem cell niche.

2022-02-20 | GSE165813 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

2022-02-20 | GSE165351 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

2022-02-20 | GSE166569 | GEO

Gene expression profile at single cell level of human cerebral cortical organoids with and without LIF treatment

Project description:Proper regulation of the proliferation and differentiation of radial glia (RG), the neural stem cells of the developing cortex, is fundamental for brain growth and organization. In humans, a specialized RG subtype, the outer radial glia (oRG), are abundant and give rise to diverse neuronal and glial progeny. However, the mechanisms regulating oRG development and differentiation are not fully understood. Here we investigated the regulation of oRG expansion and lineage potential by perturbing Leukemia Inhibitory Factor (LIF) signaling in the developing human cortex and in human pluripotent stem cell (PSC)-derived cortical organoids. LIF receptors are specifically expressed in oRG cells during neurogenesis, and, consistent with the previously described role of this cytokine as an activator of stem cell self-renewal, LIF treatment increased the number of oRG cells. Surprisingly, LIF treatment also increased the production of inhibitory interneurons (INs) in the cortex. Comparative transcriptomic analysis suggested that these INs resemble INs produced in the caudal ganglionic eminence (CGE). To test if oRG cells are the progenitors of these CGE-like INs, we isolated oRG cells from primary developing cortex and cultured them for several weeks with and without LIF treatment. We found that CGE-like INs were produced by oRG cells, and their abundance is increased by LIF treatment. Together, these observations suggest that LIF signaling regulates oRG lineage potential and capacity to generate CGE-like INs.

2023-03-23 | GSE227640 | GEO

Identity and Nature of Neural Stem Cells in the Adult Human Subventricular Zone

Project description:The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early-lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

2023-12-27 | GSE248995 | GEO

Generation of human cerebral organoids with a structured outer subventricular zone

Project description:Outer radial glia (oRG) emerged during mammalian evolution as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. The in vitro generation of oRG is essential to model and investigate the underlying mechanisms of human neocortex development and expansion. By activating the STAT3 pathway using LIF, which is not produced in guided cortical organoids, we developed a cerebral organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The structured oSVZ is composed of progenitor cells expressing specific oRG markers such as GFAP, LIFR, HOPX and closely matching human oRG in vivo. In this microenvironment, cortical neurons showed faster maturation with enhanced metabolic and functional activity. Incorporation of hPSC-derived brain vascular LIF-producing pericytes in cerebral organoids mimicked the effects of LIF treatment. These data indicate that the cellular complexity of the cortical microenvironment, including cell types of the brain vasculature, favors the appearance of oRG and provides a platform to routinely study oRG in hPSC-derived brain organoids.

2024-04-15 | GSE224346 | GEO

Single Cell Analysis Reveals Unexpected Transcriptional Heterogeneity of Neural Progenitors in the Developing Human Cortex

Project description:The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans, but virtually absent in rodents, called â??outer radial gliaâ?? (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined cell type-specific sorting with transcriptome-wide RNA-sequencing to identify genes enriched in human ORG, including targets of the transcription factor Neurogenin, and previously uncharacterized, evolutionarily dynamic, long noncoding RNAs. Single-cell transcriptional profiling of human, ferret, and mouse progenitors showed that more human RGC co-express proneural Neurogenin targets than in ferret or mouse, suggesting greater self-renewal of neuronal lineage-committed progenitors in humans. Finally, we show that activating the Neurogenin pathway in ferret RGC promotes delamination and outward migration. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors. Three biological replicates of human late mid-fetal cortex (18 to 19 weeks of gestation) were dissociated and immunolabeled. Apical and outer radial glial cells were purified by FACS and compared to an immunonegative population, predominantly neurons.

2015-02-24 | E-GEOD-66217 | biostudies-arrayexpress

Single Cell Analysis Reveals Unexpected Transcriptional Heterogeneity of Neural Progenitors in the Developing Human Cortex

Project description:The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans, but virtually absent in rodents, called ‘outer radial glia’ (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined cell type-specific sorting with transcriptome-wide RNA-sequencing to identify genes enriched in human ORG, including targets of the transcription factor Neurogenin, and previously uncharacterized, evolutionarily dynamic, long noncoding RNAs. Single-cell transcriptional profiling of human, ferret, and mouse progenitors showed that more human RGC co-express proneural Neurogenin targets than in ferret or mouse, suggesting greater self-renewal of neuronal lineage-committed progenitors in humans. Finally, we show that activating the Neurogenin pathway in ferret RGC promotes delamination and outward migration. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors.

2015-02-24 | GSE66217 | GEO

Human iPSC-derived cerebral organoids reveal progenitor pathology in EML1-linked cortical malformation

Project description:We report the single-cell RNA sequencing of day 33±2 human iPSC derived cerebral organoids harboring a CRIPSR/CAS9 mediated, heterozygous knock-out of the gene EML1 or the respective isogenic control organoids. By microdissection of several ventricular zones per organoid from 3 different batches followed by dissociation into single cells we obtained transcriptomic data of several thousand cells and we were able to identify different cell populations including RG cells (RG1), RG cells transitioning to bRG cells (RG to bRG), RG cells transitioning to neurons (RG2), intermediate progenitors and young neurons based on known marker genes (Nowakowski et al., 2017; Fan et al., 2020; Velasco et al., 2019; Pollen et al., 2015; Liu et al., 2017). When comparing the cell type composition between EML1-heKO and isogenic control-derived organoids we found a clear decrease of RG1 cells and a striking increase in the abundance of RG to bRG cells in the EML1-heKO condition, while only minor variations in the other cell clusters were observed. We further investigated molecular characteristics of the EML1-heKO derived RG to bRG cluster compared to control. Here we found a set of differentially expressed genes in the EML1-heKO compared to control. When further investigating these genes, we identified a clear upregulation of ECM and bRG markers Our data suggest that the RG to bRG cell cluster in the EML1-heKO is composed of a rather perturbed progenitor population not found as such in control organoids and most likely not reflecting a cell population present during normal human brain development.

2022-01-31 | GSE195666 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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