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Record W2280077905 · doi:10.1073/pnas.1525528113

New tools for studying microglia in the mouse and human CNS

2016· article· en· W2280077905 on OpenAlexfundno aff
Mariko L. Bennett, F. Chris Bennett, Shane A. Liddelow, Bahareh Ajami, Jennifer Zamanian, Nathaniel B. Fernhoff, Sara B. Mulinyawe, Christopher J. Bohlen, Aykezar Adil, Andrew F. Tucker, Irving L. Weissman, Edward F. Chang, Gordon Li, Gerald A. Grant, Melanie Hayden Gephart, Ben A. Barres

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2016
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsnot available
FundersNational Center for Research ResourcesNational Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeNational Institute on Drug AbuseNational Health and Medical Research CouncilNational Cancer InstituteNational Institutes of HealthNational Heart, Lung, and Blood InstituteNational Institute of Mental HealthDr. Miriam and Sheldon G. Adelson Medical Research FoundationMedical Research CouncilEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentDepartment of Health and Aged Care, Australian GovernmentMyelin Repair FoundationCanadian Institutes of Health Research
KeywordsMicrogliaBiologyNeuroscienceTransmembrane proteinCell typeAntibodyHuman brainCentral nervous systemCellImmunologyInflammationGeneticsReceptor

Abstract

fetched live from OpenAlex

The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.

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)0.003
metaresearch head score (Gemma)0.001
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: Methods · Consensus signal: Methods
Teacher disagreement score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0050.002

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 head0.136
GPT teacher head0.338
Teacher spread0.202 · 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
GenreMethods

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

Citations1,886
Published2016
Admission routes1
Has abstractyes

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