Expression profiles of subtracted mRNAs during cellular senescence in human mesenchymal stem cells derived from bone marrow

Yoo, Jung Ki; Choi, Seong–Jun; Kim, Jin Kyeoung

doi:10.1016/j.exger.2013.02.022

Cited by 21 publications

(18 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…THBS1 codes thrombospondin-1, which is secreted and incorporated into ECM [ 54 ]. We determined THBS1 upregulation in senescent hBM-MSCs in concordance with Yoo et al report [ 55 ]. PLAU gene encodes enzyme urokinase-type plasminogen activator (uPA), which regulates ECM degradation, cell adhesion, and inflammatory cell activation [ 56 ] and which activity depends on cytoskeleton reorganization [ 57 ].…”

Section: Discussionsupporting

confidence: 77%

Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow

et al. 2016

View full text Add to dashboard Cite

Human bone marrow mesenchymal stem cells (hBM-MSCs) hold promise for treating incurable diseases and repairing of damaged tissues. However, hBM-MSCs face the disadvantages of painful invasive isolation and limited cell numbers. In this study we assessed characteristics of MSCs isolated from residual human bone marrow transplantation material and expanded to clinically relevant numbers at passages 3-4 and 6-7. Results indicated that early passage hBM-MSCs are genomically stable and retain identity and high proliferation capacity. Despite the chromosomal stability, the cells became senescent at late passages, paralleling the slower proliferation, altered morphology and immunophenotype. By qRT-PCR array profiling, we revealed 13 genes and 33 miRNAs significantly differentially expressed in late passage cells, among which 8 genes and 30 miRNAs emerged as potential novel biomarkers of hBM-MSC aging. Functional analysis of genes with altered expression showed strong association with biological processes causing cellular senescence. Altogether, this study revives hBM as convenient source for cellular therapy. Potential novel markers provide new details for better understanding the hBM-MSC senescence mechanisms, contributing to basic science, facilitating the development of cellular therapy quality control, and providing new clues for human disease processes since senescence phenotype of the hematological patient hBM-MSCs only very recently has been revealed.

show abstract

Section: Discussionsupporting

confidence: 77%

Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Knockdown of FSTL1 in lung cancer cells resulted in mitotic arrest followed by apoptosis promoted by the activation of caspase-3 and −9 ( Bae et al, 2016 ). FSTL1 is downregulated during cellular senescence of human mesenchymal stem cells ( Yoo et al, 2013 ). (4) FUBP1 (far upstream element binding protein 1).…”

Section: Resultsmentioning

confidence: 99%

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

Putzbach

Gao

Patel

et al. 2017

eLife

174

View full text Add to dashboard Cite

Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that specific toxic RNAi-active sequences present in the genome can kill cancer cells.

show abstract

“…Knockdown of FSTL1 in lung cancer cells resulted in mitotic arrest followed by apoptosis promoted by the activation of caspase-3 and -9 (Bae et al, 2016). FSTL1 is downregulated during cellular senescence of human mesenchymal stem cells (Yoo, Choi, & Kim, 2013). 4) FUBP1 (far upstream element binding protein 1).…”

Section: '-A C C a A A U G U A C A A C A A A C U -5'mentioning

confidence: 99%

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

Putzbach¹,

Gao²,

Patel³

et al. 2017

Preprint

View full text Add to dashboard Cite

Over 80% of multiple tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that using specific toxic RNAi-active sequences present in the genome can kill cancer cells.

show abstract

Expression profiles of subtracted mRNAs during cellular senescence in human mesenchymal stem cells derived from bone marrow

Cited by 21 publications

References 67 publications

Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow

Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

Contact Info

Product

Resources

About