Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease [DNA methylome dataset]
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ABSTRACT:
PROVIDER: PRJNA427699 | ENA |
REPOSITORIES: ENA
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Project description: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.
2018-08-01 | GSE108562 | GEO
Project description:Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease [transcriptome dataset]
| PRJNA427698 | ENA
Project description:Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease
| PRJNA427697 | ENA
Project description: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.
2018-08-01 | GSE108563 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-08-01 | GSE108564 | GEO
Project description:Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.
| S-EPMC6286327 | biostudies-literature
Project description:In order to determine the factors that regulate senescence induction, we tried to identfy genes that are predominantly expressed in large sized senescent cells with tetraploid DNA. We sorted large or small sized HCA2 cells treated wth IR (10Gy) according to size and structure (FSC and SSC) by FACScan and analyzed global gene expression patterns.
2015-05-22 | E-GEOD-69116 | biostudies-arrayexpress
Project description:In order to determine the factors that regulate senescence induction, we tried to identfy genes that are predominantly expressed in large sized senescent cells with tetraploid DNA.
2015-05-22 | GSE69116 | GEO
Project description:The toxicity of silver and zinc oxide nanoparticles is hypothesised to be mediated by dissolved metal ions and cerium dioxide nanoparticles (CeO2 NPs) are hypothesised to induce toxicity specifically by oxidative stress dependant on their surface redox state. To test these hypotheses, RNAseq was applied to characterise the molecular responses of cells to metal nanoparticle and metal ion exposures. The human epithelial lung carcinoma cell line A549 was exposed to different CeO2 NPs with different surface charges, micron-sized and nano-sized silver particles and silver ions, micron-sized and nano-sized zinc oxide particles and zinc ions, or control conditions, for 1 hour, 6 hours and 24 hours. Concentrations were the lower of either EC20 or 128 micrograms/mL. Transcriptional responses were characterised by RNAseq transcriptomics using an Illumina HiSeq2500 .
2018-02-01 | E-MTAB-5734 | biostudies-arrayexpress
Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study Matched case-control observational study: 10 primary graft dysfunction cases vs 16 Good outcome cases. One replicate per array.
2008-09-15 | E-GEOD-9102 | biostudies-arrayexpress