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Record W2763136388 · doi:10.1038/s41598-017-13673-w

TC-PTP regulates the IL-7 transcriptional response during murine early T cell development

2017· article· en· W2763136388 on OpenAlexafffund
Kelly A. Pike, Teri Hatzihristidis, Stéphanie Bussières-Marmen, Françis Robert, Neha Desai, Diego Miranda‐Saavedra, Jerry Pelletier, Michel L. Tremblay

Bibliographic record

VenueScientific Reports · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Tyrosine Phosphatases
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersJapan Society for the Promotion of ScienceMedical Research CouncilBranco Weiss Fellowship – Society in ScienceNewcastle UniversityMcGill UniversityKishimoto FoundationJapan Science and Technology AgencyCanadian Institutes of Health ResearchEidgenössische Technische Hochschule ZürichLeukemia and Lymphoma Society
KeywordsstatBiologyCell biologyProtein tyrosine phosphataseTranscriptomeGene expressionCellular differentiationCD8Regulation of gene expressionT cellSTAT4Signal transductionProgenitor cellGeneStem cellGeneticsSTAT3Immune system

Abstract

fetched live from OpenAlex

Abstract Cytokines play a critical role in directing the discrete and gradual transcriptional changes that define T cell development. The interleukin-7 receptor (IL-7R), via its activation of the JAK-STAT pathway, promotes gene programs that change dynamically as cells progress through T cell differentiation. The molecular mechanism(s) directing differential gene expression downstream of the IL-7R are not fully elucidated. Here, we have identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as a negative regulator of IL-7R-STAT signaling in T cell progenitors, contributing to both the quantitative and qualitative nature of STAT-gene targeting. Novel genetic strategies used to modulate TC-PTP expression demonstrate that depletion of TC-PTP expression heightens the phosphorylation of STAT family members, causing aberrant expression of an interferon-response gene profile. Such molecular re-programming results in deregulation of early development checkpoints culminating in inefficient differentiation of CD4 + CD8 + double positive cells. TC-PTP is therefore shown to be required to safeguard the dynamic transcriptome necessary for efficient T cell differentiation.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies
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 score0.233
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.010
GPT teacher head0.228
Teacher spread0.218 · 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

Citations14
Published2017
Admission routes2
Has abstractyes

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