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Record W4360609907 · doi:10.21203/rs.3.rs-2051344/v1

Astrocytes express aberrant immunoglobulinsas putative gatekeeper of astrocytes to neuronal progenitor conversion

2023· preprint· en· W4360609907 on OpenAlexaff
Alice Capuz, Sylvain Osien, Mélodie‐Anne Karnoub, Soulaimane Aboulouard, Estelle Laurent, Étienne Coyaud, Antonella Raffo‐Romero, Marie Duhamel, Amélie Bonnefond, Mehdi Derhourhi, Marco Trerotola, Ikram El Yazidi‐Belkoura, David Devos, Monika Žilková, Firas Kobaissy, Fabien Vanden Abeele, Isabelle Fournier, Franck Rodet, Michel Salzet

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsPrincess Margaret Cancer Centre
FundersAgentúra na Podporu Výskumu a VývojaInstitut National de la Santé et de la Recherche MédicaleAgence Nationale de la RechercheUniversité de LilleEquipexMinistère de l'Enseignement supérieur, de la Recherche et de l'Innovation
KeywordsProgenitorProgenitor cellAstrocyteAntibodyCell biologyNeuroscienceBiologyImmunologyCentral nervous systemStem cell

Abstract

fetched live from OpenAlex

Abstract Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains as well as light chains. However, their edification is different from the ones found in B cells and resembles aberrant immunoglobulins as observed in several cancers. Moreover, the complete enzymatic V(D)J recombination complex has also been identified in astrocytes. In addition, the constant heavy chain is also present in astrocytes adult rats, whereas in primary astrocytes from human fetal astrocytes we identified constant and variable kappa chains as well as the substitution lambda chains known to be involved in pre-B cells. To gather insights into the function of these neural IgGs, CRISPR-Cas9 IgG2B constant heavy chain (IgH6), overexpression, proximal labeling of rat astrocytes IgH6 and targets identification through 2D gels were performed. In CRISPR-Cas9 IgG2B KO, overexpression of factors involved in hematopoietic cells, neural stem cells and the regulation of neuritogenesis have been identified. Moreover, overexpression of IgG2B in astrocytes induces the CRTC1-CREB-BDNF signaling pathway known to be involved in gliogenesis whereas CRISPR-Cas9 IgG2B KO triggers the BMP/YAP1/TEAD3 pathway activated in astrocytes dedifferentiation into neural progenitors. Proximal labeling experiments revealed that IgG2B is N-glycosylated by the OST complex, addressed to vesicle membranes containing the ATPase complex; and behaves partially like CD98hc through its association with LAT1. Proximity-dependent biotin labeling experiments suggest that proximal IgG2B-LAT1 interaction occurs concomitantly with MACO-1 and C2CD2L, at the heart of a potentially novel cell signaling platform. Finally, we demonstrated that these chains are synthesized individually and associated to recognize specific targets. Indeed, intermediate filaments Eif4a2 and Pdia6 involved in astrocyte fate constitute targets for these neural IgGs. Taken together, we hypotheses that aberrant neural IgG chains may act as gatekeepers of astrocytes fate.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

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 head0.138
GPT teacher head0.383
Teacher spread0.245 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations0
Published2023
Admission routes1
Has abstractyes

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