Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock

Figure 3

PPI networks for the most induced and inhibited genes in SHS-survived versus untreated eMSC. (a) PPI network for the induced genes. The network contains clusters related to cell cycle, proliferation, transcription, translation, and chromatin remodeling. It shows that SHS-survived eMSC have more active transcriptome than untreated cells. Large TP53-regulated gene cluster with many hub proteins related to tumor suppression (TP53, STK11, CDKN1a, CDKN2A, TSC2) and excision DNA repair (PARP1, SP1, PML and ERCC2) indicates that SHS-survived eMSC trigger stress protection. (b) PPI network for the inhibited genes-B containing gene cluster involved in DNA damage checkpoint coordinated by ATM, ATR, BRCA1, CHK1, and gene cluster related to chromosome segregation demonstrates DNA instability in SHS-survived eMSC. Two gene clusters related to HRAS and growth factor signaling regulated by HRAS and KRAS oncogenes and YES1, EGFR1, ERBB3, and mTOR growth factors point to the weakened prooncogenic signaling. Overall, these data are in good agreement with chromosome instability in SHS-survived cells. The network was constructed using STRING server at interaction confidence > 0.9. Clusterization was done with K-means clustering. Hub proteins, that is, the ones having more than 5 connections, are marked with multicolor large buttons; node proteins are indicated with plain small buttons.

(a)

(b)