Evidence map›Paper›PMID 40552421›Full record

ArticleCirculation2025

Mitochondrial One-Carbon Metabolism Drives CD34-Lineage Cells to Differentiate Into T Follicular Helper Cells to Form Tertiary Lymphoid Organs in Transplant Arteriosclerosis.

Xuejing Sun, Junru Wu, Tian He, Meng Yao, Li Qin, Chunyan Weng, Liping Peng, Qingzhong Xiao, Yao Lu, Hong Yuan and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026
    Review
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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

12 authors.

Xuejing Sun *Clinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).
Junru Wu *Clinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).
Tian HeClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).ORCID 0009-0005-1371-2052
Meng YaoClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).
Li QinClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).ORCID 0000-0002-8375-1234
Chunyan WengClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).
Liping PengClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).
Qingzhong XiaoCentre for Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK (Q. Xiao).ORCID 0000-0001-9101-0498
Yao LuClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).ORCID 0000-0001-6743-7870
Hong YuanClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).
Qingbo XuDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China (Q. Xu).ORCID 0000-0003-2474-8155
Jingjing CaiClinical Research Center, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (X.S., J.W., T.H., M.Y., L.Q., C.W., L.P., Y.L., H.Y., J.C.).ORCID 0000-0002-7820-536X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAllograft arteriosclerosis, a significant cause of graft failure, is linked to the formation of tertiary lymphoid organs. T follicular helper (Tfh) cells are a vital subset of helper T cells that control the formation of the germinal center in tertiary lymphoid organs. Thus, understanding the origins and regulatory mechanisms of Tfh cells in allograft arteriosclerosis is essential for developing targeted therapies.

methodsWe used a lineage-tracing strategy to track Tfh cell fate in mouse models. Single-cell RNA sequencing, flow cytometry, and immunofluorescence staining were employed to analyze cell populations in remodeled arteries 2 and 4 weeks after transplantation. Additionally, we used VEGFR-3 inhibitors and lymph node dissection to suppress lymphatic vessel formation. Metabolic signatures and flux in different cell types were investigated using ultrahigh-performance liquid chromatography and high-resolution mass spectrometry-based metabolomics. CD4

resultsCD34-lineage cells were found to be the major source of cells differentiating into T cell populations in allograft arteries. CD34-lineage cells mainly originated from the thymus, with drainage through lymphatic vessels, and differentiated into effective T cells around grafting arteries. Using CD34 lineage-tracing mice and single-cell RNA sequencing, we identified a Tfh cell population derived from CD34-lineage CD4

conclusionsThis study provides insights into the critical role of mitochondrial one-carbon metabolism and MTHFD2 in governing the differentiation of CD34-lineage cells into Tfh cells, which contributes to tertiary lymphoid organ formation in transplant vasculopathy, offering potential therapeutic targets to enhance transplant outcomes.

Indexed as

Antigens, CD34ArteriosclerosisCell DifferentiationMitochondriaTertiary Lymphoid StructuresT Follicular Helper CellsAnimalsCell LineageMiceMice, Inbred C57BLMice, KnockoutAntigens, CD34CD34-lineage cellMTHFD2one-carbon metabolismtertiary lymphoid organT follicular helper celltransplant arteriosclerosis

Identifiers

PMID40552421
PMCPMC12372736

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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.