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Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1.

Yuchen Gao | Ying Chi | Yunfei Chen | Wentian Wang | Huiyuan Li | Wenting Zheng | Ping Zhu | Jinying An | Yanan Duan | Ting Sun | Xiaofan Liu | Feng Xue | Wei Liu | Rongfeng Fu | Zhibo Han | Yingchi Zhang | Renchi Yang | Tao Cheng | Jun Wei | Lei Zhang | Xiaomin Zhang
Nature communications | 2023

Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders.

Pubmed ID: 37474525

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This is a list of tools and resources that we have found mentioned in this publication.


UniProt (tool)

RRID:SCR_002380

Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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FlowJo (tool)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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Miltenyi Biotec (tool)

RRID:SCR_008984

An Organization portal, Antibody supplier, Service resource,

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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AdipoGen (tool)

RRID:SCR_010507

An Antibody supplier,

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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BD Biosciences (tool)

RRID:SCR_013311

An Antibody supplier

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ggplot2 (tool)

RRID:SCR_014601

Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

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bcl2fastq (tool)

RRID:SCR_015058

Conversion software that both demultiplexes data and converts BCL files generated by Illumina sequencing systems to standard FASTQ file formats for downstream analysis.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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Perseus (tool)

RRID:SCR_015753

Software that supports biological and biomedical researchers in interpreting protein quantification, interaction and post-translational modification data. Perseus contains a comprehensive portfolio of statistical tools for high-dimensional omics data analysis covering normalization, pattern recognition, time-series analysis, cross-omics comparisons and multiplehypothesis testing.

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Deeptools (tool)

RRID:SCR_016366

Python based tools to process, visualize and analyse high-throughput sequencing data, such as ChIP-seq, RNA-seq or MNase-seq. Implemented within Galaxy framework. Used to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches.

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pheatmap (tool)

RRID:SCR_016418

Software tool as a function in R to draw clustered heatmaps for better control over graphical parameters.

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Metascape (tool)

RRID:SCR_016620

Web service to analyze gene or protein lists. Provides automated meta analysis tools to understand pathways within a group of orthogonal target-discovery studies.

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ProteinPilot Software (tool)

RRID:SCR_018681

Software tool for protein identification and relative protein expression analysis. Used in protein research to identify proteins and search large numbers of post translational modifications. Compatible with all proteomics MS/MS systems.

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