Detection of astrocyte epigenetic memory in in vitro systems, experimental autoimmune encephalomyelitis and multiple sclerosis samples

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The paper investigates whether previously described astrocyte pro-inflammatory “epigenetic memory” is genuine or instead caused by immune-cell contamination, after bioinformatic arguments by others suggested myeloid contamination. The authors report high astrocyte purity in both in vivo and in vitro systems, reproduce memory responses across five independent pure astrocyte in vitro models, and show dependence on the histone acetyltransferase p300. They further reanalyze five independent single-cell RNA-seq datasets from experimental autoimmune encephalomyelitis and multiple sclerosis using the Liddelow lab bioinformatic pipeline with specific purity and cell-quality criteria, detecting astrocyte epigenetic memory. The paper’s main caveat is that it relies on bioinformatic purity/cell-quality filtering and its ability to rule out contamination as the explanation. Relevance to endometriosis: the paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

We recently described astrocyte pro-inflammatory epigenetic memory based on multiple complementary in vivo and in vitro studies, and the analysis of multiple sclerosis samples. Based on bioinformatic analyses, O’Dea and Liddelow argued that the astrocyte epigenetic memory we described is the result of contamination with immune cells, particularly myeloid cells. We rebut O’Dea and Liddelow arguments as follows: (1) We show substantial purity of astrocytes analyzed in in vivo and in vitro systems; (2) We recapitulate astrocyte memory responses using five independent pure astrocyte in vitro systems, and show its dependency on the histone acetyl transferase p300; and (3) Using the Liddelow lab bioinformatic pipeline to implement purity and cell-quality criteria, we detect astrocyte epigenetic memory in five independent scRNA-seq experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) astrocyte datasets. These additional analyses and studies provide further support for the existence of astrocyte pro-inflammatory epigenetic memory.
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Abstract We recently described astrocyte pro-inflammatory epigenetic memory based on multiple complementary in vivo and in vitro studies, and the analysis of multiple sclerosis samples. Based on bioinformatic analyses, O’Dea and Liddelow argued that the astrocyte epigenetic memory we described is the result of contamination with immune cells, particularly myeloid cells. We rebut O’Dea and Liddelow arguments as follows: (1) We show substantial purity of astrocytes analyzed in in vivo and in vitro systems; (2) We recapitulate astrocyte memory responses using five independent pure astrocyte in vitro systems, and show its dependency on the histone acetyl transferase p300; and (3) Using the Liddelow lab bioinformatic pipeline to implement purity and cell-quality criteria, we detect astrocyte epigenetic memory in five independent scRNA-seq experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) astrocyte datasets. These additional analyses and studies provide further support for the existence of astrocyte pro-inflammatory epigenetic memory. Competing Interest Statement The authors have declared no competing interest.

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europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: Public-Domain