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

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Penariol, Leticia B. C., I ; Thome, Carolina H. ; Tozetti, Patricia A. ; Paier, Carlos R. K. ; Buono, Fabiana O. ; Peronni, Kamila C. ; Orellana, Maristela D. ; Covas, Dimas T. ; Moraes, Maria E. A. ; Silva, Wilson A., Jr. ; Rosa-e-Silva, Julio C. ; Ferriani, Rui A. ; Faca, Vitor M. ; Poli-Neto, Omero B. ; Tiezzi, Daniel G. ; Meola, Juliana

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 19, p. 17-pg., 2022-10-01.

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 (up arrow) and PI3K signaling via AKT to mTORC1 (down arrow in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (up arrow 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. (AU)

• FAPESP's process: 13/22431-3 - Differential transcript profile in mesenchymal stem cells obtained from the menstrual flow (MenMSCs) of women with endometriosis
• Grantee: Juliana Meola Lovato
• Support Opportunities: Research Grants - Young Investigators Grants