Evidence mapPaperPMID 42008150Full record

ArticleGigaScience2026

Integrative single-cell transcriptomics and proteomics reveal an immunometabolic framework for MSC-exosome-mediated remodeling of expanded NK cells.

Yunyun Fu, Yi Liu, Mingwen Xu, Gaojun Liu, Jianzhi Sun, Fanyu Bu, Wenqing Xie, Jiayi Zhao, Jun Luo, Qiang Guo and 6 more

Abstract read
In one paragraph

Article in GigaScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Yunyun FuCollege of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.ORCID 0009-0008-8393-4429
Yi LiuCollege of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.ORCID 0009-0006-9858-8798
Mingwen XuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou; Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.
Gaojun LiuCollege of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
Jianzhi SunCollege of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
Fanyu BuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou; Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.
Wenqing XieInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 384A Bibo Road, Pudong New Area, Shanghai 201210, China.
Jiayi ZhaoSchool of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, China.
Jun LuoCollege of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
Qiang GuoState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou; Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.
Yinghua HuangBGI Cell, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.
Fengping XuCollege of Life Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
Siqi LiuHIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 150 Dongfang Street, Xiasha Subdistrict, Hangzhou 310018, China.
Longqi LiuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou; Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.
Ying FuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou; Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.ORCID 0000-0002-3251-9849
Xuan DongState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou; Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, 203 Zhenzhong Road, Xihu District, Hangzhou 310030, China.ORCID 0000-0001-8288-322X

Funding

National Natural Science Foundation of China 32400746Science, Technology and Innovation Commission of Shenzhen Municipality JCYJ20220818102809021
6 · The paper itself

Abstract

backgroundNatural killer (NK) cells play a central role in anti-tumor immunity and immunosurveillance of senescence, yet their clinical performance is frequently limited by functional exhaustion during ex vivo expansion. Mesenchymal stem cell-derived exosomes (MSC-Exos) are increasingly recognized as immunomodulators, but their broader effects on NK cell fitness and functional states remain incompletely characterized.

resultsHere, we assessed MSC-Exos-mediated regulation of human NK cells using a standardized ex vivo priming platform integrated with single-cell transcriptomics and proteomic profiling. MSC-Exos significantly improved NK cell viability in a dose- and time-dependent manner while preserving a CD56⁺CD3- NK cell-enriched phenotype. MSC-Exos-treated NK cells showed enhanced cytotoxicity against K562 tumor cells and senescent fibroblasts. This phenotype was accompanied by increased expression of the activating receptors NKG2D and CD16, reduced LAG3 expression, and enhanced granzyme B expression and degranulation. Consistent with improved NK cell fitness, MSC-Exos treatment was also associated with upregulated expression of genes involved in NRF2-linked redox programs and improved mitochondrial readouts in NK cells. Single-cell analyses of MSC-Exos-treated NK cells revealed enhanced immune-effector programs and reduced inflammatory stress, while trajectory inference indicated that MSC-Exos may bias the NK cell state distribution toward more cytotoxic effector-like states. Proteomic profiling of MSC-Exos identified enrichment of FcγR-associated signaling components, supporting the hypothesis that exosomal composition may be related to the FcγR/CD16-associated transcriptional and phenotypic features observed in MSC-Exos-treated NK cells.

conclusionsOur data indicate that MSC-Exos improve NK cell viability and functional fitness during ex vivo expansion and bias NK cells toward a more effector-cytotoxic state. Together, these findings provide an immunometabolic framework for MSC-Exos-assisted NK cell manufacturing while underscoring the need for further causal validation.

Indexed as

ExosomesKiller Cells, NaturalMesenchymal Stem CellsProteomicsTranscriptomeCytotoxicity, ImmunologicGranzymesHumansK562 CellsSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisGranzymeseffector-cytotoxic stateimmunometabolic frameworkmesenchymal stem cell-derived exosomesnatural killer cellssingle-cell transcriptomics

Identifiers

PMID42008150
PMCPMC13273429

What Socratic holds

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LicenceCC BY
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.