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Record W4411035423 · doi:10.1101/2025.05.30.657119

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

2025· preprint· en· W4411035423 on OpenAlexaff
Hong‐Gyun Lee, Zhaorong Li, Camilo Faust Akl, Joon-Hyuk Lee, Gavin Piester, Jack P. Antel, Veit Rothhammer, Michael A. Wheeler, Alexandre Prat, Iain C. Clark, Francisco J. Quintana

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicImmune responses and vaccinations
Canadian institutionsCentre Hospitalier de l’Université de MontréalMcGill UniversityMontreal Neurological Institute and Hospital
Fundersnot available
KeywordsExperimental autoimmune encephalomyelitisMultiple sclerosisAstrocyteEpigeneticsEncephalomyelitisNeuroscienceIn vitroNeuroinflammationImmunologyBiologyMedicineCentral nervous systemGeneticsGeneInflammation

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.283
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.218
Teacher spread0.201 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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