ArticleAging cell2023
Heterochromatic silencing of immune-related genes in glia is required for BBB integrity and normal lifespan in drosophila.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
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- Tumour-host interactions in Drosophila: mechanisms in the tumour micro- and macroenvironment.Molecular oncology · 2026Review
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- Transcriptional complexity in the insect central complex: single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts.bioRxiv : the preprint server for biology · 2025Article
- Assessing the feasibility of using salivary microRNAs as biomarkers to distinguish between chronic stress and childhood trauma in African American young women in an exploratory pilot study.Frontiers in psychiatry · 2025Article
- Article
- Heterochromatic silencing of immune-related genes in glia is required for BBB integrity and normal lifespan in drosophila.Aging cell · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
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Abstract
Glia and neurons face different challenges in aging and may engage different mechanisms to maintain their morphology and functionality. Here, we report that adult-onset downregulation of a Drosophila gene CG32529/GLAD led to shortened lifespan and age-dependent brain degeneration. This regulation exhibited cell type and subtype-specificity, involving mainly surface glia (comprising the BBB) and cortex glia (wrapping neuronal soma) in flies. In accordance, pan-glial knockdown of GLAD disrupted BBB integrity and the glial meshwork. GLAD expression in fly heads decreased with age, and the RNA-seq analysis revealed that the most affected transcriptional changes by RNAi-GLAD were associated with upregulation of immune-related genes. Furthermore, we conducted a series of lifespan rescue experiments and the results indicated that the profound upregulation of immune and related pathways was not the consequence but cause of the degenerative phenotypes of the RNAi-GLAD flies. Finally, we showed that GLAD encoded a heterochromatin-associating protein that bound to the promoters of an array of immune-related genes and kept them silenced during the cell cycle. Together, our findings demonstrate a previously unappreciated role of heterochromatic gene silencing in repressing immunity in fly glia, which is required for maintaining BBB and brain integrity as well as normal lifespan.
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