Format

Send to

Choose Destination
Sci Rep. 2017 Dec 19;7(1):17837. doi: 10.1038/s41598-017-16224-5.

Identification of new genes associated to senescent and tumorigenic phenotypes in mesenchymal stem cells.

Author information

1
Faculdade de Ciências da Saúde do Trairi (FACISA), Universidade Federal do Rio Grande do Norte (UFRN), Rua Traíri, S/N, Centro, Santa Cruz, Rio Grande do Norte (RN), 59200-000, Brazil.
2
Laboratório de Biologia Molecular e Genômica, Centro de Biociências, UFRN, Campus Universitário, Avenida Senador Salgado Filho, 3000, Lagoa nova, Natal, RN, 59078-900, Brazil.
3
Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, CCS/UFRN, Av General Cordeiro de Farias S/N, Petropolis, Natal, 59010-115, RN, Brazil.
4
Instituto do Cérebro, Instituto de Metrópole Digital, UFRN, Av. Nascimento de Castro, 2155, UFRN, 59056-450, RN, Brazil.
5
Laboratório de Biologia Molecular e Genômica, Centro de Biociências, UFRN, Campus Universitário, Avenida Senador Salgado Filho, 3000, Lagoa nova, Natal, RN, 59078-900, Brazil. sbatistu@cb.ufrn.br.

Abstract

Although human mesenchymal stem cells (hMSCs) are a powerful tool for cell therapy, prolonged culture times result in replicative senescence or acquisition of tumorigenic features. To identify a molecular signature for senescence, we compared the transcriptome of senescent and young hMSCs with normal karyotype (hMSCs/n) and with a constitutional inversion of chromosome 3 (hMSC/inv). Senescent and young cells from both lineages showed differentially expressed genes (DEGs), with higher levels in senescent hMSCs/inv. Among the 30 DEGs in senescent hMSC/inv, 11 are new candidates for biomarkers of cellular senescence. The functional categories most represented in senescent hMSCs were related to cellular development, cell growth/proliferation, cell death, cell signaling/interaction, and cell movement. Mapping of DEGs onto biological networks revealed matrix metalloproteinase-1, thrombospondin 1, and epidermal growth factor acting as topological bottlenecks. In the comparison between senescent hMSCs/n and senescent hMSCs/inv, other functional annotations such as segregation of chromosomes, mitotic spindle formation, and mitosis and proliferation of tumor lines were most represented. We found that many genes categorized into functional annotations related to tumors in both comparisons, with relation to tumors being highest in senescent hMSCs/inv. The data presented here improves our understanding of the molecular mechanisms underlying the onset of cellular senescence as well as tumorigenesis.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center