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| Status |
Public on Aug 01, 2018 |
| Title |
Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease [transcriptome dataset] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Mesenchymal stem-cells (MSCs) are of particular interest for treating immune-related diseases due to their immunosuppressive capacities. Here, we show that Small sized MSCs primed with Hypoxia and Calcium ion (SHC-MSCs) exhibit the enhanced functions regarding stemness and immunomodulation for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord-blood MSCs, SHC-MSCs were resistant to the passage dependent cellular senescence mediated by MCP-1 and p53/p21 cascade and highly secreted the pro-angiogenic and immune-modulatory factors, resulting in suppression of T-cell proliferation. Genome-wide DNA methylome and transcriptome analysis indicate that SHC-MSCs characteristically up-regulated immune-modulation, cell adhesion and cell-cycle related genes. As downstream factors, PLK1, ZNF143, DHRS3, and FOG2 proteins played a key role on the beneficial effects of SHC-MSCs, evidenced by the promoted self-renewal, migration, pro-angiogenic, anti-inflammatory, and T cell suppression capacities in their-over-expressing MSCs. Importantly, administration of SHC-MSCs or PLK1-over-expressing cells (PLK1-MSCs) significantly reduced the symptoms of graft-versus-host disease (GVHD) in a humanized mouse model which led to significantly improved survival, less weight loss, and less histopathologic injuries of GVHD target organs compared with naive MSC-infused mice. Collectively, our study suggests that small-sized MSCs primed with hypoxia could advance the therapeutic strategy for the clinical treatment of allogeneic conflicts including GVHD.
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| Overall design |
Human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) were normally maintained (NT) or cultivated by SHC procedure (SHC) which enriched small sized cells and at the same time primed with hypoxia ( 3 % oxygen) and calcium ion (1.8 mM). Total RNA from three independent replicates was isolated using the RNeasy Mini Kit (QIAGEN, Valencia, CA), including treatment with DNase I (QIAGEN). One ug of total RNA was used for the Affymetrix GeneChip Human 2.0 ST Array (Affymetrix, Santa Clara, CA), in accordance with the manufacturer’s instructions.
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| Contributor(s) |
Shin D, Kim Y, Ju H |
| Citation(s) |
29789652 |
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| Submission date |
Dec 27, 2017 |
| Last update date |
Mar 15, 2019 |
| Contact name |
DONG-MYUNG SHIN |
| E-mail(s) |
d0shin03@amc.seoul.kr
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| Phone |
82-2-3010-2086
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| Organization name |
University of Ulsan College of Medicine
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| Department |
Department of Biomedical Sciences
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| Street address |
Pungnap-2 dong, Songpa-gu
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| City |
Seoul |
| ZIP/Postal code |
05505 |
| Country |
South Korea |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE108564 |
Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease |
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| Relations |
| BioProject |
PRJNA427698 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108563_RAW.tar |
29.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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