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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
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lncRNA 3222401L13Rik/ENSG00000272070 modulates microglial inflammatory programs in association with PU.1
Ranjit Pradhan1, M Sadman Sakib1, Lalit Kaurani1
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Long non-coding RNA (lncRNA) 3222401L13Rik modulates microglial inflammation and phagocytosis. Its reduced expression in Alzheimer's disease brains suggests it as a therapeutic target for neuroinflammation.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Long non-coding RNAs (lncRNAs) regulate brain function, but their role in microglial aging and neurodegenerative diseases is unclear.
- The non-coding RNAome offers therapeutic discovery potential beyond protein-coding genes.
- The lncRNA 3222401L13Rik is upregulated in aging mouse hippocampus.
Purpose of the Study:
- Investigate the function of the glia-enriched lncRNA 3222401L13Rik and its human homolog ENSG00000272070 in microglia.
- Determine the role of this lncRNA in microglial aging and neuroinflammation.
- Explore its potential as a therapeutic target for neurodegenerative diseases like Alzheimer's disease.
Main Methods:
- Knockdown of 3222401L13Rik in primary mouse microglia.
- RNA-sequencing to analyze transcriptional changes.
- Analysis of human induced pluripotent stem cell (iPSC)-derived microglia.
- Investigation of interaction with transcription factor PU.1.
- Analysis of postmortem Alzheimer's disease brain tissue.
Main Results:
- Knockdown of 3222401L13Rik increased pro-inflammatory cytokines and phagocytic activity in microglia.
- RNA-seq revealed enrichment of TNF and complement signaling pathways.
- Human homolog ENSG00000272070 showed conserved functions in iPSC-derived microglia.
- 3222401L13Rik interacts with the transcription factor PU.1.
- ENSG00000272070 expression was reduced in Alzheimer's disease brains.
Conclusions:
- 3222401L13Rik/ENSG00000272070 is a conserved, aging-associated lncRNA regulating microglial inflammatory states via PU.1.
- This lncRNA links glial regulation to Alzheimer's disease-related neuroinflammation.
- 3222401L13Rik represents a potential molecular target for modulating microglial activity in neurodegenerative diseases.
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