Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE189227 | GEO | 2022/07/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease [bulk RNA-seq]

Project description:Microglia are critical for brain development and play a central role in Alzheimer’s disease (AD) etiology. Down syndrome (DS), also known as trisomy 21, is the most common genetic origin of intellectual disability and the most common risk factor for AD. Surprisingly, little information is available on the impact of trisomy of human chromosome 21 (Hsa21) on microglia in DS brain development and AD in DS (DSAD). Using our new induced pluripotent stem cell (iPSC)-based human microglia-containing cerebral organoid and chimeric mouse brain models, here we report that DS microglia exhibit enhanced synaptic pruning function during brain development. Consequently, electrophysiological recordings demonstrate that DS microglial mouse chimeras show impaired synaptic neurotransmission, as compared to control microglial chimeras. Upon being exposed to human brain tissue-derived soluble pathological tau, DS microglia display dystrophic phenotypes in chimeric mouse brains, recapitulating microglial responses seen in human AD and DSAD brain tissues. Further flow cytometry, single-cell RNA-sequencing, and immunohistological analyses of chimeric mouse brains demonstrate that DS microglia undergo cellular senescence and exhibit elevated type I interferon signaling after being challenged by pathological tau. Mechanistically, we find that shRNA-mediated knockdown of Hsa21-encoded type I interferon receptor genes, IFNARs, rescues the defective DS microglial phenotypes both during brain development and in response to pathological tau. Our findings provide in vivo evidence supporting a paradigm shifting theory that human microglia respond to pathological tau with accelerated senescence. Our results further suggest that targeting IFNARs may improve microglial functions during DS brain development and prevent human microglial senescence in DS individuals with AD.

2022-07-08 | GSE189225 | GEO

Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease [single-cell RNA-seq]

2022-07-08 | GSE189226 | GEO

Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease

Project description:Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease

| PRJNA782002 | ENA

Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models

Project description: Not available

| S-EPMC8561005 | biostudies-literature

Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease [bulk RNA-seq]

Project description:Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease [bulk RNA-seq]

| PRJNA782007 | ENA

Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease [single-cell RNA-seq]

Project description:Type I Interferon Signaling Mediates Microglial Dysfunction and Senescence in Human-Mouse Chimeric Brain Models of Down Syndrome and Alzheimer’s Disease [single-cell RNA-seq]

| PRJNA782006 | ENA

OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome.

Project description: Not available

| S-EPMC6944064 | biostudies-literature

LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies.

Project description: Not available

| S-EPMC8100991 | biostudies-literature

Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease.

Project description: Not available

| S-EPMC4721948 | biostudies-literature

Linking In Vitro Models of Endothelial Dysfunction with Cell Senescence.

Project description: Not available