Microglia-derived TGF-β1 ligand maintains microglia homeostasis via autocrine mechanism and is critical for normal cognitive function in adult mouse brain
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA988467 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25052167_1.fastq.gz | Fastqsanger.gz | |||
| SRR25052167_2.fastq.gz | Fastqsanger.gz | |||
| SRR25052168_1.fastq.gz | Fastqsanger.gz | |||
| SRR25052168_2.fastq.gz | Fastqsanger.gz | |||
| SRR25052169_1.fastq.gz | Fastqsanger.gz |
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Project description:While TGF-β signaling is essential for microglial function, the cellular source of TGF-β ligand and its spatial regulation remains unclear in the adult CNS. Our data support that microglia, not astrocytes or neurons, are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia (MG)-Tgfb1 inducible knockout (iKO) leads to the activation of microglia featuring a dyshomeostatic transcriptomic profile that resembles disease-associated microglia (DAMs), injury-associated microglia, and aged microglia, suggesting that microglial self-produced TGF-β1 ligands are important in the adult CNS. Interestingly, astrocytes in MG-Tgfb1 iKO mice show a transcriptome profile that closely aligns with A1-like astrocytes. Additionally, using sparse mosaic single-cell microglia iKO of TGF-β1 ligand, we established an autocrine mechanism for TGF-β signaling. Importantly MG-Tgfb1 iKO mice show cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is critical for the maintenance of brain homeostasis and normal cognitive function in the adult brain.
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