TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment

Sandra Isenmann, Agnieszka Arthur, Andrew C W Zannettino, Jenna L. Turner, Shi Songtao, Carlotta A. Glackin, Stan Gronthos

Research output: Contribution to journalArticlepeer-review

150 Citations (Scopus)

Abstract

The TWIST family of basic helix-loop-helix transcription factors, Twist-1 and Dermo-1 are known mediators of mesodermal tissue development and contribute to correct patterning of the skeleton. In this study, we demonstrate that freshly purified human bone marrow-derived mesenchymal stromal/stem cells (MSC) express high levels of Twist-1 and Dermo-1 which are downregulated following ex vivo expansion. Enforced expression of Twist-1 or Dermo-1 in human MSC cultures increased expression of the MSC marker, STRO-1, and the early osteogenic transcription factors, Runx2 and Msx2. Conversely, overexpression of Twist-1 and Dermo-1 was associated with a decrease in the gene expression of osteoblast-associated markers, bone morphogenic protein-2, bone sialoprotein, osteopontin, alkaline phosphatase and osteocalcin. High expressing Twist-1 or Dermo-1 MSC lines exhibited an enhanced proliferative potential of approximately 2.5-fold compared with control MSC populations that were associated with elevated levels of Id-1 and Id-2 gene expression. Functional studies demonstrated that high expressing Twist-1 and Dermo-1 MSC displayed a decreased capacity for osteo/chondrogenic differentiation and an enhanced capacity to undergo adipogenesis. These findings implicate the TWIST gene family members as potential mediators of MSC self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development.

Original languageEnglish
Pages (from-to)2457-2468
Number of pages12
JournalStem Cells
Volume27
Issue number10
DOIs
Publication statusPublished or Issued - Oct 2009

Keywords

  • Adipocytes
  • Chondrocytes
  • Dermo-1
  • Mesenchymal stem cell
  • Osteoblasts
  • Stromal cells
  • Twist

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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