Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

APOE-isogenic iPSC-derived astrocytes

ABSTRACT: APOE-isogenic iPS cells were differentiated into astrocytes and analyzed for APOE genotype-mediated metabolic differences.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Christian Tackenberg

PROVIDER: MSV000097390 | MassIVE | Thu Mar 20 15:13:00 GMT 2025

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

APOE-Ɛ4 astrocytes exhibit deficits in endocytic uptake that contribute to the delayed maturation of neuronal network activity and alter neuronal tau uptake in co-cultures of human iPSC-derived brain cells

Project description:To explore the mechanistic basis of ApoE Ɛ4 vs ApoE Ɛ3 protein expression on endocytic pathways responsible for tau uptake in neurons and astrocytes and the maturation of neuronal networks, we have developed genotype matched co-cultures of iPSC derived astrocytes and neurons derived from isogenic triads of iPSC lines generated by the ADAPTED consortium (Schmid et al., 2019, 2020) . We show that isogenic iPSC derived APOE-E4 expressing astrocytes take up less extracellular tau than APOE-E3 or APOE null astrocytes, while isogenic neurons in monoculture take up equivalent amounts of tau primarily through macropinocytosis. Co-culture of neurons with genotype matched astrocytes increases the general uptake capacity of neurons by increasing the dependence of neuronal endocytosis on dynamin mediated pathways. Co-culture also enhances the emergence of spontaneous neuronal activity; however, the emergence of synchronous network activity is impaired by the expression of APOE-E4 genotype. We performed RNA-Seq on the astrocytes, neurons and co-cultures to understand the molecular pathway changes associated with different ApoE genotypes.

2024-04-08 | GSE171700 | GEO

APOE4-dependent transcriptome changes in human iPSC-derived astrocytes

Project description:APOE4 genotype is the strongest risk factor for the pathogenesis of sporadic Alzheimer’s disease (AD), but the detailed molecular mechanism of APOE4-mediated synaptic impairment remains to be determined in human cellular context. In this study, we generated human astrocyte model carrying APOE3 or APOE4 genotype using human induced pluripotent stem cells (iPSCs), in which isogenic APOE4 iPSCs were genome-edited from healthy control APOE3 iPSCs. By transcriptome analysis of human astrocytes between APOE genotypes, we showed the upregulation of an extracellular matrix glycoprotein in human APOE4 astrocytes, which may cause synaptic degeneration in concert with the equivocal reactive character and lipid change. Together, these results demonstrate novel negative impact of human APOE4 astrocyte on synaptic integrity and lead to a promising therapeutic intervention into APOE4-carriers.

2023-08-31 | GSE206314 | GEO

APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes (Spatial)

Project description:Apolipoprotein 4 (APOE4), is the strongest genetic risk allele associated with the development of late onset Alzheimer’s disease (AD). Across the CNS, astrocytes are the predominant expressor of Apoe while also being critical mediators of neuroinflammation and cerebral metabolism. APOE4 has been consistently linked with dysfunctional neuro-immunometabolism, however insights into the molecular constituents driving these responses remain unclear. Utilizing complimentary approaches across humanized ApoE expressing mice and isogenic IPS astrocytes, we demonstrate that harboring ApoE4 alters astrocyte immunometabolic response to pro-inflammatory stimuli. Our findings demonstrate that ApoE4-expressing astrocytes acquire distinct transcriptional repertoires at the single-cell and spatially-resolved domains, which driven, in-part, by preferential utilization of the cRel transcription factor. Further, inhibiting cRel translocation abrogated inflammatory-induced glycolytic shift and ultimately resulted in significantly dampened glycolysis-associated metabolites in tandem with mitigating production of multiple pro-inflammatory cytokines. Altogether, our findings elucidate novel cellular underpinnings by which ApoE4 drives maladaptive immunometabolic responses of astrocytes.

2022-10-20 | GSE215445 | GEO

APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes (scRNA-Seq)

2022-10-20 | GSE215444 | GEO

APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes (bulk RNA-Seq)

2022-10-20 | GSE215446 | GEO

APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia

Project description:The major genetic risk factor for Alzheimer’s disease (AD), APOE4, accelerates beta-amyloid (Aβ) plaque formation, but whether this is caused by APOE expressed in microglia or astrocytes is debated. We express here the human APOE isoforms in astrocytes in an Apoe-deficient AD mouse model. This is not only sufficient to restore the amyloid plaque pathology but also induces the characteristic transcriptional pathological responses in Apoe-deficient microglia surrounding the plaques. We find that both APOE4 and the protective APOE2 from astrocytes increase fibrillar plaque deposition, but differentially affect soluble Aβ aggregates. Microglia and astrocytes show specific alterations in function of APOE genotype expressed in astrocytes. Our experiments indicate a central role of the astrocytes in APOE mediated amyloid plaque pathology and in the induction of associated microglia responses.

2024-10-04 | GSE252454 | GEO

RNA-Seq from Primate iPSC derived Astrocytes (iAstrocytes)

Project description:RNA-Seq experiment to detect transcriptional differences in iPSC derived astrocytes between 3 primate species, humans, chimpanzees and macaques. The goal of the experiment is to characterise genome-wide evolutionary changes in transcriptional and regulatory systems across the primate lineage in astrocytes

2025-03-06 | E-MTAB-13252 | biostudies-arrayexpress

Proteomic signatures of schizophrenia-sourced iPSC-derived astrocytes

Project description:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. ??Molecular and functional abnormalities in astrocytes play a role in the etiology and pathogenesis of schizophrenia. In this study, human induced pluripotent stem cells (hiPSC)-derived astrocytes from schizophrenia patients were investigated regarding their proteome, inflammatory responses, and their secretome effect on vascularization. Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Taken together, our results suggest that schizophrenia astrocytes are immunologically dysfunctional which might affect vascularization through secreted factors.

2023-04-27 | PXD031640 | Pride

iPSC-Derived Cholangiocytes

Project description:Human iPS cells were differentiated to cholangiocyte-like cells thorugh five phases of endodermal differentiation.

2016-08-25 | GSE86007 | GEO

Gene expression analysis of astrocytes differentiated from iPS cells generated from the fibroblasts of PSEN1deltaE9 mutant AD and their isogenic control iPS lines

Project description:Gene expression analysis of astrocytes differentiated from iPS cells generated from the fibroblasts of PSEN1deltaE9 mutant AD and their isogenic control iPS lines

| PRJNA576835 | ENA

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