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| Status |
Public on Apr 15, 2024 |
| Title |
Defining Mesenchymal Stem/Stromal Cell-Induced Myeloid-Derived Suppressor Cells Using Single-Cell Transcriptomics |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mesenchymal stem/stromal cells (MSCs) modulate the immune response through interactions with innate immune cells. We previously demonstrated that MSCs alleviate ocular autoimmune inflammation by directing BM cell differentiation from pro-inflammatory CD11bhiLy6ChiLy6Glo cells into immunosuppressive CD11bmidLy6CmidLy6Glo cells. Herein, we analyzed MSC-induced CD11bmidLy6Cmid cells using single-cell RNA sequencing and compared them with CD11bhiLy6Chi cells. Our investigation revealed 7 distinct immune cell types including myeloid-derived suppressor cells (MDSCs) in the CD11bmidLy6Cmid cells, while CD11bhiLy6Chi cells included mostly monocytes/macrophages with a small cluster of neutrophils. These MSC-induced MDSCs highly expressed Retnlg, Cxcl3, Cxcl2, Mmp8, Cd14 and Csf1r as well as Arg1. Comparative analyses of CSF-1RhiCD11bmidLy6Cmid and CSF-1RloCD11bmidLy6Cmid cells demonstrated that the former had a homogeneous monocyte morphology and produced elevated levels of IL-10. Functionally, these CSF-1RhiCD11bmidLy6Cmid cells, compared with the CSF-1RloCD11bmidLy6Cmid cells, inhibited CD4+ T cell proliferation and promoted CD4+CD25+Foxp3+ Treg expansion in culture and in a mouse model of experimental autoimmune uveoretinitis. RELM-γ encoded by Retnlg, one of the highly-upregulated genes in MSC-induced MDSCs, had no direct effects on T cell proliferation, Treg expansion or splenocyte activation. Together, our study revealed a distinct transcriptional profile of MSC-induced MDSCs and identified CSF-1R as a key cell-surface marker for detection and therapeutic enrichment of MDSCs.
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| Overall design |
We purified CD11bmidLy6Cmid cells from BM cells cocultured with MSCs as well as CD11bhiLy6Chi cells from BM cells without MSC coculture by fluorescence-activated cell sorting (FACS), and subjected these two FACS-sorted live cell populations to scRNA-seq using the 10x Genomics Chromium platform.
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| Web link |
http://10.1016/j.ymthe.2024.04.026
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| Contributor(s) |
Lee H, Oh J |
| Citation(s) |
38627968 |
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| Submission date |
Apr 08, 2024 |
| Last update date |
Jul 16, 2024 |
| Contact name |
Joo Youn Oh |
| E-mail(s) |
jooyounoh77@gmail.com
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| Phone |
821086394920
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| Organization name |
Seoul National University College of Medicine
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| Department |
Ophthalmology
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| Lab |
Joo Youn Oh
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| Street address |
103 Daehakro, Jongrogu, Yeongondong
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| City |
Seoul |
| State/province |
Korea, Republic of |
| ZIP/Postal code |
03080 |
| Country |
South Korea |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
| GSM8190843 |
CD11bhiLy6Chi cells from bone marrow (BM) cells without human mesenchymal stem/stromal cells (MSC) coculture |
| GSM8190844 |
CD11bmidLy6Cmid cells from bone marrow (BM) cells cocultured with human mesenchymal stem/stromal cells (MSCs) |
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| Relations |
| BioProject |
PRJNA1097466 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE263397_RAW.tar |
48.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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