What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

月经血来源间充质干细胞的转录组和蛋白质组能告诉我们关于子宫内膜异位症的哪些信息?

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作者:Letícia B C Penariol ,Carolina H Thomé ,Patrícia A Tozetti ,Carlos R K Paier ,Fabiana O Buono ,Kamila C Peronni ,Maristela D Orellana ,Dimas T Covas ,Maria E A Moraes ,Wilson A Silva Jr ,Júlio C Rosa-E-Silva ,Rui A Ferriani ,Vitor M Faça ,Omero B Poli-Neto ,Daniel G Tiezzi ,Juliana Meola

Abstract

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓ in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (↑ in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis. Keywords: MenSCs; endometriosis; expression profile; menstrual blood; multi-omics.

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