Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microglia lineage relaxation towards a lymphoid-like state protects against Alzheimer’s disease.

ABSTRACT: Microglia lineage relaxation towards a lymphoid-like state protects against Alzheimer’s disease.

PROVIDER: PRJNA1148425 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Microglia lineage relaxation towards a lymphoid-like state protects against Alzheimer’s disease.

Project description:Amyloid plaques, a hallmark of Alzheimer's disease (AD), combine chemical and physical properties foreign to normal brain tissue. These "non-self" plaque patterns trigger local tissue responses in the brain, including microglia activation. Microglial response to the plaques can be both protective, aiming at amyloid clearance and neuroprotection, and harmful, associated with microglia-driven inflammation and neurotoxicity. Here, we provide evidence that the microglial neuroprotective response to amyloid plaques involves a relaxation of the microglia lineage specification toward a lymphoid-like state. We found that a subpopulation of plaque-associated microglia downregulates the microglia lineage-specifying transcription factor PU.1 and de-represses several lymphoid-expressed genes, including those that play a key role in receptor-mediated signaling in B and T lymphocytes. The shift toward the lymphoid lineage is associated with an increased signaling capacity of PU.1low microglia that supports microglia maintenance at the plaque. Functionally, we show that PU.1low microglia protect neurons and reduce plaque-associated damage in a mouse model of amyloid deposition. Engineered genetic downregulation of PU.1 in microglia in the healthy brain emulates phenotypic features of plaque-associated microglia, promotes microglia-plaque association in disease, and protects against the loss of functional neuronal connections and associated behaviors, including cognition and memory in mice. We propose that the plaque-induced microglia lineage relaxation represents a novel mechanism of the microglial responses in the presence of AD pathology that is adaptive in nature and protective by function.

2025-08-07 | GSE274896 | GEO

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease.

Project description:Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease.

| PRJNA1148985 | ENA

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease

Project description:Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease

| PRJNA1260427 | ENA

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease. [RNA-seq]

Project description:Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease. [RNA-seq]

| PRJNA1261018 | ENA

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease

Project description:Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer’s disease (AD). The microglial response to amyloid plaques can be either neuroprotective or neurotoxic. Here we show that the protective function of microglia is associated with and functionally linked to a transcriptional shift toward lymphoid gene expression. Microglial contact with the plaques induces downregulation of PU.1, a lineage-specifying transcription factor. PU.1 downregulation plays a key role in mitigating the severity of AD, as evidenced by a reduction in neurotoxic microglia activation, preservation of neuronal connections, maintenance of cognitive function, and increased survival in mice with genetically reduced PU.1 expression in microglia. The neuroprotective effect of PU.1 downregulation is linked to the de-repression of lymphoid-specific proteins, particularly CD28—a surface protein critical for T cell activation. Microglia-specific deficiency in CD28, which is expressed exclusively in a small subset of plaque-associated PU.1low microglia, promotes an inflammatory microglial state and associated increase in amyloid plaque load. Our findings suggest that PU.1low lymphoid/CD28-expressing microglia that emerge in response to AD pathology exert a suppressive, anti-inflammatory effect during AD. This novel role of CD28 -and potentially other lymphoid co-stimulatory or co-inhibitory receptor proteins- in governing microglia responses in AD points to possible new immunotherapy approaches for AD treatment.

2025-08-07 | GSE296641 | GEO

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease.

2025-08-07 | GSE275026 | GEO

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer’s disease. [RNA-seq]

2025-08-07 | GSE296769 | GEO

Plaque induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer's disease

2025-08-07 | PXD063383 | Pride

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer's disease

Project description:Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer's disease

| PRJNA1259806 | ENA

Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer's disease [scRNA-seq]

Project description:Plaque-induced transcriptional reprogramming of microglia towards lymphoid receptor expression protects against Alzheimer's disease [scRNA-seq]

| PRJNA1261025 | 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