Research Paper Volume 13, Issue 7 pp 9991—10014
Transcriptome and lipidome profile of human mesenchymal stem cells with reduced senescence and increased trilineage differentiation ability upon drug treatment
- 1 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, Heilongjiang, China
- 2 National & Local Joint Engineering Laboratory for Animal Models of Human Diseases, First Hospital, Jilin University, Changchun 130021, China
- 3 Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
- 4 State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing 100875, China
- 5 School of Pharmacy, Qiqihar Medical University, Qiqihar 161000, Heilongjiang, China
- 6 BeiGene (Beijing) Co., Ltd, Beijing 102206, China
Received: December 9, 2020 Accepted: February 3, 2021 Published: March 26, 2021https://doi.org/10.18632/aging.202759
How to Cite
Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Human Mesenchymal stem cells (hMSCs) are multi-potential cells which are widely used in cell therapy. However, the frequently emerged senescence and decrease of differentiation capabilities limited the broad applications of MSC. Several strategies such as small molecules treatment have been widely studied and used to improve the stem characteristics bypassing the senescence but the exact mechanisms for them to reduce senescence have not been fully studied. In this study, hMSCs were treated by rapamycin, oltipraz, metformin, and vitamin C for the indicated time and these cells were subjected to senescence evaluation and trilineage differentiation. Furthermore, transcriptomics and lipidomics datasets of hMSCs after drug treatment were analyzed to interpret biological pathways responsible for their anti-senescence effects. Although four drugs exhibited significant activities in promoting MSC osteogenic differentiation, metformin is the optimal drug to promote trilineage differentiation. GO terms illustrated that the anti-aging effects of drugs were mainly associated with cellular senescence, mitotic and meiosis process. Biosynthesis of phosphatidylcholines (PC) and phosphatidylethanolamine (PE) were inhibited whereas production of phosphatidylinositols (PIs) and saturated fatty acids (SFA)/ mono-unsaturated fatty acids (MUFA) conversion was activated. Medium free fatty acids (FFA) was increased in hMSCs with different anti-aging phenotypes. Therefore, we established a comprehensive method in assessing drug intervention based on the results of transcriptomics and lipidomics. The method can be used to study different biological phenotypes upon drug intervention in MSC which will extend the clinical application of hMSCs.
hMSC: human mesenchymal stem cell; GO: gene ontology; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; SFA: saturated fatty acid; MUFA: mono-unsaturated fatty acid; FFA: free fatty acid; FDA: Food and Drug Administration; BM: bone marrow; LC-MS: liquid chromatography - mass spectrometry; SA-β-gal: senescence-associated-β-galactosidase; DEG: differentially expressed gene; LPC: lysophosphatidylcholine; LPE: lysophosphatidylethanolamine; PS: phosphatidylserine; Cer: Ceramide; SM: sphingomyelin; DG: diacylglyceride; TG: triacylglyceride; FFA: free fatty acid; CDS1: CDP-Diacylglycerol Synthase 1; LCAT: lecithin cholesterol acyl transferase; LPCAT: lysophosphatidylcholine acyltransferase; SCD: stearoyl-CoA desaturase; COVID-19: novel coronavirus disease 2019; GPL: glycerophospholipid; NAFLD: nonalcoholic fatty liver disease; TPM: transcript per million; PBS: phosphate buffer saline.