CD49f enhances multipotency and maintains stemness through the direct regulation of OCT4 and SOX2

Stem Cells. 2012 May;30(5):876-87. doi: 10.1002/stem.1052.


CD49f (integrin subunit α6) regulates signaling pathways in a variety of cellular activities. However, the role of CD49f in regulating the differentiation and pluripotency of stem cells has not been fully investigated. Therefore, in this study, human mesenchymal stem cells (hMSCs) were induced to form spheres under nonadherent culture conditions, and we found that the CD49f-positive population was enriched in MSC spheres compared with MSCs in a monolayer. The expression of CD49f regulated the ability of hMSCs to form spheres and was associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Furthermore, the forced expression of CD49f modulated the proliferation and differentiation potentials of hMSCs through prolonged activation of PI3K/AKT and suppressed the level of p53. We showed that the pluripotency factors OCT4 and SOX2 were recruited to the putative promoter region of CD49f, indicating that OCT4 and SOX2 play positive roles in the expression of CD49f. Indeed, CD49f expression was upregulated in human embryonic stem cells (hESCs) compared with hMSCs. The elevated level of CD49f expression was significantly decreased upon embryoid body formation in hESCs. In hESCs, the knockdown of CD49f downregulated PI3K/AKT signaling and upregulated the level of p53, inducing differentiation into three germ layers. Taken together, our data suggest that the cell-surface protein CD49f has novel and dynamic roles in regulating the differentiation potential of hMSCs and maintaining pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology
  • Cells, Cultured
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation / physiology
  • Humans
  • Integrin alpha6 / biosynthesis*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Octamer Transcription Factor-3 / biosynthesis*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • SOXB1 Transcription Factors / biosynthesis*
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / metabolism


  • Integrin alpha6
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt