Evidence map›Paper›PMID 41026602›Full record

ArticleCell reports2025

Biphasic control of the B cell transcriptome by mTORC1 and GSK3.

Jens Kalchschmidt, Tomoya Kanno, Solji Park, Wendy D Dubois, Yongbing Zhao, Pawel Trzaskoma, Craig J Thomas, Louis M Staudt, John J O'Shea, Seolkyoung Jung and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. The role of mTORC2/RICTOR in immune cells and inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jens KalchschmidtNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: jens.kalchschmidt@nih.gov.
Tomoya KannoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Solji ParkNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Wendy D DuboisNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Yongbing ZhaoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Pawel TrzaskomaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Craig J ThomasNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Louis M StaudtNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
John J O'SheaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: john.oshea@nih.gov.
Seolkyoung JungNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Rafael CasellasNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: rcasellas@mdanderson.org.

Funding

Stat transcription factors in immunoregulation and autoimmune diseaseZIAAR041159 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$49.3M
RAG and AID biologyZIAAR041148 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$44.8M
Intramural NIH HHS ZIA AR041148Intramural NIH HHS ZIA AR041159
6 · The paper itself

Abstract

A central question in immune regulation is how cells coordinate transcriptional responses to environmental cues. It remains unclear whether transcriptional regulation is controlled by isolated mechanism or integrated regulatory programs. Here, we develop a high-sensitivity, genome-wide CRISPR-Cas9 screening platform with 47 transcriptional reporters in human B cell lymphoma, identifying 4,440 regulators and 17,638 regulatory interactions. To enable the exploration of these networks, we establish B-LEARN, an interactive portal for data visualization and discovery. Our results reveal a large number of shared regulators across our 47 screens that act as context-dependent activators or repressors. Globally, we uncover a biphasic regulatory architecture in which mTORC1 and GSK3 exert opposing control over the B cell transcriptome. Notably, mTOR inhibition broadly activates key B cell genes, an effect antagonized by GSK3. Thus, B cell transcription is governed by an integrated, pathway-driven circuit, offering new targets to modulate gene expression in lymphoma and autoimmune disease.

Indexed as

B-LymphocytesGlycogen Synthase Kinase 3Mechanistic Target of Rapamycin Complex 1TranscriptomeCell Line, TumorCRISPR-Cas SystemsHumansLymphoma, B-CellGlycogen Synthase Kinase 3Mechanistic Target of Rapamycin Complex 1CP: Immunologyfunctional CRISPR screensgene regulatory networkGSK3human B cell lymphomaimmune response gene expressionmTORreporter cell linessmall-molecule screeningtranscriptional regulation

Identifiers

PMID41026602
PMCPMC12594101

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.