Specific mesothelial signature marks the heterogeneity of mesenchymal stem cells from high-grade serous ovarian cancer

TY - JOUR

T1 - Specific mesothelial signature marks the heterogeneity of mesenchymal stem cells from high-grade serous ovarian cancer

AU - Verardo, Roberto

AU - Piazza, Silvano

AU - Klaric, Enio

AU - Ciani, Yari

AU - Bussadori, Giulio

AU - Marzinotto, Stefania

AU - Mariuzzi, Laura

AU - Cesselli, Daniela

AU - Beltrami, Antonio P.

AU - Mano, Miguel

AU - Itoh, Masayoshi

AU - Kawaji, Hideya

AU - Lassmann, Timo

AU - Carninci, Piero

AU - Hayashizaki, Yoshihide

AU - Forrest, Alistair R.R.

AU - Beltrami, Carlo A.

AU - Schneider, Claudio

N1 - Publisher Copyright: © 2014 AlphaMed Press.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Mesenchymal stem/stromal cells (MSCs) are the precursors of various cell types that compose both normal and cancer tissue microenvironments. In order to support the widely diversified parenchymal cells and tissue organization, MSCs are characterized by a large degree of heterogeneity, although available analyses of molecular and transcriptional data do not provide clear evidence. We have isolated MSCs from high-grade serous ovarian cancers (HG-SOCs) and various normal tissues (N-MSCs), demonstrated their normal genotype and analyzed their transcriptional activity with respect to the large comprehensive FANTOM5 sample dataset. Our integrative analysis conducted against the extensive panel of primary cells and tissues of the FANTOM5 project allowed us to mark the HG-SOC-MSCs CAGE-seq transcriptional heterogeneity and to identify a cell-type-specific transcriptional activity showing a significant relationship with primary mesothelial cells. Our analysis shows that MSCs isolated from different tissues are highly heterogeneous. The mesothelial-related gene signature identified in this study supports the hypothesis that HG-SOC-MSCs are bona fide representatives of the ovarian district. This finding indicates that HG-SOC-MSCs could actually derive from the coelomic mesothelium, suggesting that they might be linked to the epithelial tumor through common embryological precursors.

AB - Mesenchymal stem/stromal cells (MSCs) are the precursors of various cell types that compose both normal and cancer tissue microenvironments. In order to support the widely diversified parenchymal cells and tissue organization, MSCs are characterized by a large degree of heterogeneity, although available analyses of molecular and transcriptional data do not provide clear evidence. We have isolated MSCs from high-grade serous ovarian cancers (HG-SOCs) and various normal tissues (N-MSCs), demonstrated their normal genotype and analyzed their transcriptional activity with respect to the large comprehensive FANTOM5 sample dataset. Our integrative analysis conducted against the extensive panel of primary cells and tissues of the FANTOM5 project allowed us to mark the HG-SOC-MSCs CAGE-seq transcriptional heterogeneity and to identify a cell-type-specific transcriptional activity showing a significant relationship with primary mesothelial cells. Our analysis shows that MSCs isolated from different tissues are highly heterogeneous. The mesothelial-related gene signature identified in this study supports the hypothesis that HG-SOC-MSCs are bona fide representatives of the ovarian district. This finding indicates that HG-SOC-MSCs could actually derive from the coelomic mesothelium, suggesting that they might be linked to the epithelial tumor through common embryological precursors.

KW - Adult stem cells

KW - Cancer

KW - Cell biology

KW - Genomics

KW - Mesenchymal stem cells

KW - Tissue-specific stem cells

UR - http://www.scopus.com/inward/record.url?scp=84907904181&partnerID=8YFLogxK

U2 - 10.1002/stem.1791

DO - 10.1002/stem.1791

M3 - Article

C2 - 25069783

AN - SCOPUS:84907904181

SN - 1066-5099

VL - 32

SP - 2998

EP - 3011

JO - Stem Cells

JF - Stem Cells

IS - 11

ER -