Identification of senescence-associated genes in human bone marrow mesenchymal stem cells.
Human bone marrow mesenchymal stem cells (hBMMSCs) are multipotent stem cells that can differentiate into several specialized cell types, including bone, cartilage, and fat cells. The proliferative capacity of hBMMSCs paves the way for the development of regenerative medicine and tissue engineering. However, long-term in vitro culture of hBMMSCs leads to a reduced life span of the cells due to senescence, which leads eventually to growth arrest. To investigate the molecular mechanism behind the cellular senescence of hBMMSCs, microarray analysis was used to compare the expression profiles of early passage hBMMSCs, late passage hBMMSCs and hBMMSCs ectopically expressing human telomerase reverse transcriptase (hTERT). Using an intersection analysis of 3892 differentially expressed genes (DEGs) out of 27,171 total genes analyzed, we identified 338 senescence-related DEGs. GO term categorization and pathway network analysis revealed that the identified genes are strongly related to known senescence pathways and mechanisms. The genes identified using this approach will facilitate future studies of the mechanisms underlying the cellular senescence of hBMMSCs.
Ryu
Eunsook
E
Macrogen Inc., World Meridian Venture Center, 60-24, Gasan-dong, Seoul 153-023, Republic of Korea.
Hong
Su
S
Kang
Jaeku
J
Woo
Junghoon
J
Park
Jungjun
J
Lee
Jongho
J
Seo
Jeong-Sun
JS
D001854:Bone Marrow Cells / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019098:Telomerase / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D019098:Telomerase