Breast cancer resistance protein identifies clonogenic keratinocytes in human interfollicular epidermis

Stem Cell Res Ther. 2015 Mar 24;6(1):43. doi: 10.1186/s13287-015-0032-2.


Introduction: There is a practical need for the identification of robust cell-surface markers that can be used to enrich for living keratinocyte progenitor cells. Breast cancer resistance protein (ABCG2), a member of the ATP binding cassette (ABC) transporter family, is known to be a marker for stem/progenitor cells in many tissues and organs.

Methods: We investigated the expression of ABCG2 protein in normal human epidermis to evaluate its potential as a cell surface marker for identifying and enriching for clonogenic epidermal keratinocytes outside the pilosebaceous tract.

Results: Immunofluorescence and immunoblotting studies of human skin showed that ABCG2 is expressed in a subset of basal layer cells in the epidermis. Flow cytometry analysis showed approximately 2-3% of keratinocytes in non-hair-bearing epidermis expressing ABCG2; this population also expresses p63, β1 and α6 integrins and keratin 14, but not CD34, CD71, C-kit or involucrin. The ABCG2-positive keratinocytes showed significantly higher colony forming efficiency when co-cultured with mouse 3T3 feeder cells, and more extensive long-term proliferation capacity in vitro, than did ABCG2-negative keratinocytes. Upon clonal analysis, most of the freshly isolated ABCG2-positive keratinocytes formed holoclones and were capable of generating a stratified differentiating epidermis in organotypic culture models.

Conclusions: These data indicate that in skin, expression of the ABCG2 transporter is a characteristic of interfollicular keratinocyte progentior cells and suggest that ABCG2 may be useful for enriching keratinocyte stem cells in human interfollicular epidermis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Epidermal Cells*
  • Epidermis / metabolism
  • Epidermis / transplantation
  • Fluorescent Antibody Technique
  • Humans
  • Immunoblotting
  • Integrin alpha6 / metabolism
  • Integrin beta1 / metabolism
  • Keratin-14 / metabolism
  • Keratinocytes / cytology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / metabolism*
  • Skin / cytology
  • Stem Cells / cytology*
  • Transplantation, Heterologous


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Biomarkers
  • CKAP4 protein, human
  • Integrin alpha6
  • Integrin beta1
  • KRT14 protein, human
  • Keratin-14
  • Membrane Proteins
  • Neoplasm Proteins