Role of slug transcription factor in human mesenchymal stem cells

Elena Torreggiani, Gina Lisignoli, Cristina Manferdini, Elisabetta Lambertini, Letizia Penolazzi, Renata Vecchiatini, Elena Gabusi, Pasquale Chieco, Andrea Facchini, Roberto Gambari, Roberta Piva

Research output: Contribution to journalArticle

Abstract

The pathways that control mesenchymal stem cells (MSCs) differentiation are not well understood, and although some of the involved transcription factors (TFs) have been characterized, the role of others remains unclear. We used human MSCs from tibial plateau (TP) trabecular bone, iliac crest (IC) bone marrow and Wharton's jelly (WJ) umbilical cord demonstrating a variability in their mineral matrix deposition, and in the expression levels of TFs including Runx2, Sox9, Sox5, Sox6, STAT1 and Slug, all involved in the control of osteochondroprogenitors differentiation program. Because we reasoned that the basal expression level of some TFs with crucial role in the control of MSC fate may be correlated with osteogenic potential, we considered the possibility to affect the hMSCs behaviour by using gene silencing approach without exposing cells to induction media. In this study we found that Slug-silenced cells changed in morphology, decreased in their migration ability, increased Sox9 and Sox5 and decreased Sox6 and STAT1 expression. On the contrary, the effect of Slug depletion on Runx2 was influenced by cell type. Interestingly, we demonstrated a direct in vivo regulatory action of Slug by chromatin immunoprecipitation, showing a specific recruitment of this TF in the promoter of Runx2 and Sox9 genes. As a whole, our findings have important potential implication on bone tissue engineering applications, reinforcing the concept that manipulation of specific TF expression levels may elucidate MSC biology and the molecular mechanisms, which promote osteogenic differentiation.

Original languageEnglish
Pages (from-to)740-751
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number4
DOIs
Publication statusPublished - 2012

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Keywords

  • Gene silencing
  • Human mesenchymal stem cells
  • Osteogenesis
  • Slug
  • Transcription factors

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Torreggiani, E., Lisignoli, G., Manferdini, C., Lambertini, E., Penolazzi, L., Vecchiatini, R., Gabusi, E., Chieco, P., Facchini, A., Gambari, R., & Piva, R. (2012). Role of slug transcription factor in human mesenchymal stem cells. Journal of Cellular and Molecular Medicine, 16(4), 740-751. https://doi.org/10.1111/j.1582-4934.2011.01352.x