Evidence map›Paper›PMID 38489349›Full record

ArticleScience immunology2024

Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics.

Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu and 10 more

Open access · greenAbstract read
In one paragraph

Article in Science immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
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

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Review
  3. Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. NAD + metabolism and function in innate and adaptive immune cells.Journal of inflammation (London, England) · 2025
    Review
  11. Article
  12. Mitochondrial response to fever boosts TImmunometabolism (Cobham, Surrey) · 2025
    Article
  13. Article
  14. Article
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

20 authors at 4 institutions in 1 country.

Lucien TurnerDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0001-6612-9745
Tran Ngoc Van LeDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-0342-2634
Eric CrossDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0003-0482-5969
Clemence QueriaultDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0009-0003-4835-8386
Montana KnightDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-5229-4122
Krittin TrihemasavaDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-4017-1256
James DavisDepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Patrick SchaeferCenter for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Janet NguyenDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0009-0008-3291-0945
Jimmy XuCenter of Excellence in Environmental Toxicology and Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-8437-8411
Brian GoldspielDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0001-5762-8868
Elise HallDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Kelly RomeDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-0703-1788
Michael ScaglioneDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0003-2953-1748
Joel EggertDivision of Immunology, Lowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0002-2982-6020
Byron Au-YeungDivision of Immunology, Lowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0002-6446-9102
Douglas C WallaceCenter for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Clementina MesarosCenter of Excellence in Environmental Toxicology and Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-5117-2038
Joseph A BaurDepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-8262-6549
Will BailisDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0001-9420-6250
Children's Hospital of Philadelphia · USEmory University · USTranslational Therapeutics (United States) · USUniversity of Pennsylvania · US

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and AgingR01DK098656 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Joseph A. Baur · 2013 to 2026
$6.1M
Regulation of CD4 T cell tolerance by the NR4A family of nuclear receptorsR01AI165706 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JULIE ZIKHERMAN · 2022 to 2026
$3.0M
TRANSFUSION MEDICINE RESEARCH TRAINING PROGRAMT32HL007775 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SIEGEL, DONALD LAWRENCE · 1993 to 2023
$2.8M
Stress-modified growth signaling in dynamic nutrient environmentsR35GM138085 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI Will H. Bailis · 2020 to 2026
$2.7M
Understanding the roles of cardiac NAD pools and therapeutic effects of precursor supplements in heart failureR01HL165792 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BAUR, JOSEPH A. · 2022 to 2025
$2.7M
Training in Microbial Pathogenesis and GenomicsT32AI141393 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GOULIAN, MARK D, ZHU, JUN · 2019 to 2023
$1.3M
The biochemical basis of immune cell reprogramming: how cellular metabolism regulates epigenetic remodeling during T cell differentiationK22AI141758 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BAILIS, WILL H. · 2019 to 2020
$270k
Elucidating the Regulation and Requirement of the NAD salvage pathway in CD8+ T Cell ExhaustionF31CA261156 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TURNER, LUCIEN · 2021 to 2023
$136k
NCI NIH HHS F31 CA261156NCI NIH HHS T32 CA009140NHLBI NIH HHS R01 HL165792NHLBI NIH HHS T32 HL007775NIAID NIH HHS K22 AI141758NIAID NIH HHS R01 AI165706NIAID NIH HHS T32 AI141393NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK098656NIEHS NIH HHS P30 ES013508NIGMS NIH HHS R35 GM138085
6 · The paper itself

Abstract

Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity-dependent metabolome. Through this central anabolic role, we found that NAD biosynthesis governs a quiescence exit checkpoint, thereby pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities, and enhancing NAD biosynthesis permits the expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) could predict division potential for both T and B cells, before the first division, unmixing proliferative heterogeneity. We believe that this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.

Indexed as

LymphocytesNADMetabolomeSignal TransductionNAD

Identifiers

PMID38489349
PMCPMC11064129
OpenAlexW4392857181

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.