Copyright ©The Author(s) 2020.
World J Stem Cells. Sep 26, 2020; 12(9): 966-985
Published online Sep 26, 2020. doi: 10.4252/wjsc.v12.i9.966
Table 1 Summary of various transcriptomics analyses studies of senescent mesenchymal stem cells
Ref.SpeciesTissue sourcesClassificationCellsGroupsDatabaseDifferentially expressed genes (DEGs)Identification of targets
Benisch et al[48], 2012HumanBone marrow of femoral headsAffymetrix Gene ChipCultured in DMEM/Ham’s F-12 (1:1) medium supplemented with 10% fetal calf serum (FCS), 1 U/mL penicillin, 100 μg/mL streptomycin, and 50 μg/mL L-ascorbic acid 2-phosphate. Used after 1 to 2 passageshMSC-C: Middle-aged donors (42-67 yr old); hMSC-old: The age-matched control group (79-89 yr old); hMSC-OP: Patients (79-94 yr old) who had primary osteoporosis; hMSC-senescent: Healthy donors of middle-age (42-64 yr old) until they entered senescenceGEO accession numbers: GSE35955; GSE35956; GSE35957; GSE35958; GSE35959One gene was upregulated and seven downregulated in all three groups, compared with the hMSC-C group; 38 genes with enhanced and 36 genes with reduced expression in hMSC-OP and hMSC-old groups, compared with hMSC-C; 2477 genes with higher and 1222 genes with lower expression in hMSC-OP, in comparison with hMSC-oldThe reliable or promising candidates for osteoporosis, including susceptibility genes: Lrp5, Spp1 (Osteopontin), Col1a1, Sost, and Mab21l1
Yoo et al[50], 2013HumanBone marrow-derived MSCsSSH analysisPurchased from Cambrex Bio ScienceYoung human MSCs (Y-hMSCs): Approximately 10 population doubling levels (PDL); senescent MSCs (S-hMSCs): Until approximately 30 PDL, at least 80% of the cells were positive for SA-β-Gal stainingNANineteen genes were down-regulated and 43 upregulated in S-hMSCsGradually downregulated mRNA in S-hMSCs: Pdia3, Wdr1, Fstl1, Copg1, Lman1, and Pdia6; significantly upregulated genes: Hsp90b1, Eid1, Atp2b4, Ddah1, Prnp, Rab1a, Psg5, Tm4sf1, and Ssr3
Bustos et al[52], 2014MouseBone marrowAffymetrix Gene ChipSorted by fluorescence-activated cell sorting (FACS)BM-MSCs from young (3-mo-old) and aged (24-mo-old) mice; young donor BM-MSCs vs aged onesGEO accession number: GSE44403927 genes were differentially expressedConfirmed by qPCR: Cytokine receptors (15 genes), chemokines (Ccr7, Cxc3cr1, Cxcr5), markers of cell senescence (CDK, p21, p27, and p53), Marcks, Mmp9, and Timp2
Duscher et al [54], 2014MouseInguinal fat padsMicrofluidic-based single-cell gene expression platformCD45-/CD31-/CD34+ cells were sortedAdipose-derived mesenchymal stem cells (ADSCs) from young (3 mo) and aged (21 mo) miceNADifferences in transcriptional profiles of genes related to cell stemness, remodeling, and vasculogenesis: Adam10, Angpt1, Angpt2, Hif1a, Mef2c, and Sod2Age-related depletion of a subpopulation of MSCs characterized by a pro-vascular transcriptional profile, such as Angpt1, Vegfa, and Sod3
Medeiros et al[19], 2017HumanUmbilical cord veinsThe GeneChip Human Genome U133 Plus 2.0 arrayThe surface markers including CD105, CD73, CD90, CD14, CD34, and CD45 were analyzed by flow cytometry; differentiation capacity toward three lineages was assessedhMSCs in the 9th (Y-hMSCs) and 18th passages (S-hMSCs) were used for assays, hMSCs/n from the donor with normal karyotype, and hMSCs/inv from the donor with a constitutional inversion of chromosome 3; the comparisons were as follows: (1) Y-hMSCs/n & S-hMSC/n; (2) Y-hMSCs/inv & S-hMSCs/inv; (3) Y-hMSCs/n & Y-hMSCs/inv; and (4) S-hMSCs/n & S-hMSCs/invGEO accession number: GSE5653073 DEGs in S-hMSCs/n compared with Y-hMSCs/n and 279 DEGs in S-hMSCs/inv compared with Y-hMSCs/inv; 93 DEGs in Y-hMSCs/inv compared with Y-hMSCs/n; 425 DEGs in S-hMSCs/inv compared with S-hMSCs/n. The candidates for senescent markers: Dio2, Foxe1, Galnt5, Has3, Krt19, Krt34, Krtap1-55, Oc730755, Mrvi1, Plcb4, and Scube3Confirmed by qPCR: Ankrd1 and Mmp1 in S-hMSC/n vs Y-hMSC/n; Sfrp1, Ankrd1, G0s2, and Ndn in S-hMSC/inv vs Y-hMSC/inv; Adora2b, Sfrp1, Kynu, G0s2, Aldh1a1, and Mab21l1 in Y-hMSC/inv vs Y-hMSC/inv; and Adora2b, Ccl7, Sfrp1, Kynu, Ankrd1, Mmp1, Lamc2, G0s2, M ab21l1, and Ndn in S-hMSC/inv vs S-hMSC/n
Wu et al[49], 2019HumanBone marrow of femoral headsAffymetrix Gene ChipCultured in DMEM/Ham’s F-12 (1:1) medium supplemented with 10% FCS, 1 U/mL penicillin, 100 μg/mL streptomycin, and 50 μg/mL L-ascorbic acid 2-phosphate. used after 1 to 2 passagesMiddle-aged group vs elderly groupGEO accession number: GSE35955156 up-regulated and 343 down-regulated differentially expressed genes (DEGs)Six hub genes identified by PPI network analysis: Ctnnb1, Ppp2r1a, Fyn, Mapk1, Pik3c2a and Ep300. 11 TFs identified by TFs screening: Creb1, Cux1, Egr1, Ep300, Foxc1, Hsf2, Mef2a, Plau, Sp1, Stat1 and Usf1
Wiese et al[47], 2019HumanThe perivascular region of Wharton’s jelly from umbilical cordsAffymetrix GeneChip U133A 2.0 arraysProvided by Tissue Regeneration Therapeutics, Inc. Positive for the cell surface markers CD73, CD90, CD105, CD10, CD140b, CD146 (40%-60%), CD166, and MHC-I; negative for the cell surface markers CD45, CD31, CD34, and HLA-DR. Exhibit trilineage potential in directed differentiation assaysHuman umbilical cord perivascular cells (HUCPVCs) from early passages (P2–P5), mid-passages (P6–P9), and pre-senescent passages (P10–P12)GEO accession number: GSE119987The transcriptome of HUCPVCs was stable through P5. A single significantly DE gene was identified at P6 and P7 compared with P2, whereas 5 DE genes were detected at P8 and 27 at P9. The number of significantly DE probe sets increased from 27 (P9) to 301 (P10), then to 1094 (P12)Significant transcriptome drift occurred only after P5
Leveque et al[51], 2019HumanBone marrow aspirates from the iliac crest of healthy donors (21 to 26 years old)RNAseq AnalysisThe surface markers including CD34, CD45, CD73, CD90, and CD105 were analyzed by flow cytometry; differentiation capacity toward three lineages was assessedFour groups: Control MSCs (P3); 21 d pesticide mixture exposed MSCs (P4); long-term cultivated MSCs (P14); and MSCs from aging donor (72 yr old)The SRA database under accession number PRJNA510912394, 1073, and 2077 EST were significantly increased from pesticide exposed, P14 MSCs, and MSC from aged donor; 218, 1077, and1571 ESTs were down-regulatedConfirmed by QPCR: Igf-1, Prolactin, Leptin, and Cox-2