Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1

نویسندگان

  • Luisa Cironi
  • Paolo Provero
  • Nicola Riggi
  • Michalina Janiszewska
  • Domizio Suva
  • Mario-Luca Suva
  • Vincent Kindler
  • Ivan Stamenkovic
چکیده

BACKGROUND A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism. METHODOLOGY/PRINCIPAL FINDINGS We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression. CONCLUSIONS/SIGNIFICANCE Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Expression of the FUS-CHOP fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma.

A subset of sarcomas is associated with specific chromosomal translocations that give rise to fusion genes believed to participate in transformation and oncogenesis. Identification of the primary cell environment that provides permissiveness for the oncogenic potential of these fusion genes is essential to understand sarcoma pathogenesis. We have recently shown that expression of the EWS-FLI-1 ...

متن کامل

SYT-SSX1 and SYT-SSX2 interfere with repression of E-cadherin by snail and slug: a potential mechanism for aberrant mesenchymal to epithelial transition in human synovial sarcoma.

Synovial sarcoma is a primitive mesenchymal neoplasm characterized in almost all cases by a t(X;18) fusing the SYT transcriptional coactivator gene with either SSX1 or SSX2, with the resulting fusion gene encoding an aberrant transcriptional regulator. A subset of synovial sarcoma, predominantly cases with the SYT-SSX1 fusion, shows foci of morphologic epithelial differentiation in the form of ...

متن کامل

P-88: Comparing Epigenetic Profile of Oct4 Regulatory Region in Embryonal Carcinoma Cells under Retinoic Acid Induction

Background: Embryonal carcinoma (EC) cells derived from germ cell tumors are valuable tools for investigating differentiation and developmental biology processes in vitro. The advantage of the reproducible and rapid expansion of these cell lines provides a useful alternative to embryos for the study of mammalian cell differentiation. During early stages of cell differentiation, the rate of tran...

متن کامل

Evaluation of Changes in Global DNA Methylation during Osteoblastic Differentiation of Mesenchymal Stem Cells: A Laboratory Study

Background and Objectives: Control processes in osteoblastic differentiation of mesenchymal stem cells are not yet fully understood. Epigenetic mechanisms, especially the methylation of CpG Islands in the promoter of genes, are considered as one of the most important control mechanisms in stem cell differentiation. In the process of differentiation, it is debated whether only the methylation of...

متن کامل

A New Two Step Induction Protocol for Neural Differentiation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Background: In this study, we examined a new two step induction protocol for improving the differentiation of human umbilical cord blood-derived mesenchymal stem cells into neural progenitor cells. Materials and Methods: Human umbilical cord blood-derived mesenchymal stem cells were first cultured in Dulbecco’s modified eagle medium supplemented with 10% fetal bovine serum in a humidified incu...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2009