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Article

Gene Expression Profile of Human Mesenchymal Stromal Cells Exposed to Hypoxic and Pseudohypoxic Preconditioning—An Analysis by RNA Sequencing

1
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland
2
Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland
3
Department of Medical Genetics, Medical University of Warsaw, Pawińskiego 3C, 02-106 Warsaw, Poland
4
Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warsaw, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Sonia Rocha
Int. J. Mol. Sci. 2021, 22(15), 8160; https://doi.org/10.3390/ijms22158160
Received: 30 June 2021 / Revised: 24 July 2021 / Accepted: 26 July 2021 / Published: 29 July 2021
Mesenchymal stromal cell (MSC) therapy is making its way into clinical practice, accompanied by research into strategies improving their therapeutic potential. Preconditioning MSCs with hypoxia-inducible factors-α (HIFα) stabilizers is an alternative to hypoxic priming, but there remains insufficient data evaluating its transcriptomic effect. Herein, we determined the gene expression profile of 6 human bone marrow-derived MSCs preconditioned for 6 h in 2% O2 (hypoxia) or with 40 μM Vadadustat, compared to control cells and each other. RNA-Sequencing was performed using the Illumina platform, quality control with FastQC and adapter-trimming with BBDUK2. Transcripts were mapped to the Homo_sapiens. GRCh37 genome and converted to relative expression using Salmon. Differentially expressed genes (DEGs) were generated using DESeq2 while functional enrichment was performed in GSEA and g:Profiler. Comparison of hypoxia versus control resulted in 250 DEGs, Vadadustat versus control 1071, and Vadadustat versus hypoxia 1770. The terms enriched in both phenotypes referred mainly to metabolism, in Vadadustat additionally to vesicular transport, chromatin modifications and interaction with extracellular matrix. Compared with hypoxia, Vadadustat upregulated autophagic, phospholipid metabolism, and TLR cascade genes, downregulated those of cytoskeleton and GG-NER pathway and regulated 74 secretory factor genes. Our results provide valuable insight into the transcriptomic effects of these two methods of MSCs preconditioning. View Full-Text
Keywords: mesenchymal stem cells; MSCs; hypoxic priming; PHDs inhibitor; Vadadustat; HIF-1α; transcriptional regulation; RNA-Seq mesenchymal stem cells; MSCs; hypoxic priming; PHDs inhibitor; Vadadustat; HIF-1α; transcriptional regulation; RNA-Seq
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MDPI and ACS Style

Zielniok, K.; Burdzinska, A.; Murcia Pienkowski, V.; Koppolu, A.; Rydzanicz, M.; Zagozdzon, R.; Paczek, L. Gene Expression Profile of Human Mesenchymal Stromal Cells Exposed to Hypoxic and Pseudohypoxic Preconditioning—An Analysis by RNA Sequencing. Int. J. Mol. Sci. 2021, 22, 8160. https://doi.org/10.3390/ijms22158160

AMA Style

Zielniok K, Burdzinska A, Murcia Pienkowski V, Koppolu A, Rydzanicz M, Zagozdzon R, Paczek L. Gene Expression Profile of Human Mesenchymal Stromal Cells Exposed to Hypoxic and Pseudohypoxic Preconditioning—An Analysis by RNA Sequencing. International Journal of Molecular Sciences. 2021; 22(15):8160. https://doi.org/10.3390/ijms22158160

Chicago/Turabian Style

Zielniok, Katarzyna, Anna Burdzinska, Victor Murcia Pienkowski, Agnieszka Koppolu, Malgorzata Rydzanicz, Radoslaw Zagozdzon, and Leszek Paczek. 2021. "Gene Expression Profile of Human Mesenchymal Stromal Cells Exposed to Hypoxic and Pseudohypoxic Preconditioning—An Analysis by RNA Sequencing" International Journal of Molecular Sciences 22, no. 15: 8160. https://doi.org/10.3390/ijms22158160

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