Evidence map›Paper›PMID 41462339›Full record

ArticleGenome medicine2025

Single-cell RNA-seq analysis of longitudinal CD4

Rahul Biradar, Ubaid Ullah Kalim, Tapio Lönnberg, Sini Junttila, Tomi Suomi, Sebastián Zúñiga Norman, Inna Starskaia, Niklas Paulin, Lea Mikkola, Outi Vaarala and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 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. 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

14 authors.

Rahul BiradarTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Ubaid Ullah KalimTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland. ubaull@utu.fi.
Tapio LönnbergTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Sini JunttilaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Tomi SuomiTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Sebastián Zúñiga NormanTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Inna StarskaiaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Niklas PaulinTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Lea MikkolaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Outi VaaralaOrion Pharma, Espoo, Finland.
Omid RasoolTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Mikael KnipTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Laura L Elo *Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland. laura.elo@utu.fi.
Riitta Lahesmaa *Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland. rilahes@utu.fi.

Funding

Trial to Reduce IDDM in the Genetically at Risk StudyU01HD040364 · NICHD · UNIVERSITY OF HELSINKI · PI KNIP, MIKAEL · 2001 to 2015
$32.7M
Trial to Reduce IDDM in the Genetically at Risk: A Nutritional primary preventionU01HD042444 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECKER, DOROTHY J · 2001 to 2015
$24.4M
Trial to Reduce IDDM in the Genetically at Risk (TRIGR) Data Management UnitU01HD051997 · NICHD · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2006 to 2015
$7.1M
Trial to Reduce IDDM in the Genetically at Risk (TRIGR) Data Management UnitR01HD051997 · NICHD · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2016 to 2018
$2.3M
European Research Council ERC 677943European Union's Horizon 2020 research and innovation programme 955321InFLAMES Flagship Programme 337530NICHD NIH HHS R01 HD051997NICHD NIH HHS U01 HD040364NICHD NIH HHS U01 HD042444NICHD NIH HHS U01 HD051997NIH HHS HD040364, HD042444, HD051997Novo Nordisk Fonden NNF19OC0057218Research Council of Finland 250114, 292335, 294337, 292482, 319280, 329277, 331793, 335435, 31444Research Council of Finland 310561, 314443, 329278, 335434, 335611, 341342
6 · The paper itself

Abstract

backgroundT cells play a pivotal role in the autoimmune destruction of beta cells in type 1 diabetes. However, our understanding of the disease has been limited by lack of a comprehensive single-cell transcriptome analysis of T cells during its early stages.

methodsWe performed single cell RNA sequencing analysis of 73 longitudinal CD4

resultsBy phenotypically characterizing over 99,000 cells, we identified cell-type-specific gene expression patterns associated with disease progression. While the cell-type compositions were similar, several genes were differentially regulated in cases in different cell types. Besides pathways altered in cases in specific cell types, interferon related pathways and pathways related to viral response were altered in multiple cell types in cases. We also identified gene regulatory networks (regulon) that drives the transcriptional state of the cell types. Notably, we observed increased PRDM1 regulon activity in Th17 cells and diminished GATA3 regulon activity in naïve T cells, among other changes in the activity of different regulons in children progressing to disease.

conclusionsOur findings reveal early, cell-type-specific changes in transcription and gene regulatory networks in CD4⁺ T cells associated with type 1 diabetes progression, highlighting key pathways and transcriptional regulators. These insights provide a foundation for understanding early immune dysregulation in type 1 diabetes and basis for strategies to develop early diagnosis and intervention.

Indexed as

CD4-Positive T-LymphocytesDiabetes Mellitus, Type 1Single-Cell AnalysisChild, PreschoolFemaleGene Expression ProfilingHumansInfantLongitudinal StudiesMaleMulticenter Studies as TopicRandomized Controlled Trials as TopicRNA-SeqSingle-Cell Gene Expression AnalysisTranscriptomeCD4+ T cellsRegulonsSeroconversionSingle-cell RNA sequencing scRNA-seqType 1 diabetes (T1D)

Identifiers

PMID41462339
PMCPMC12751217

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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.