title: Breast cancer resistance protein identifies clonogenic keratinocytes in human interfollicular epidermis.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Plastic, Reconstructive & Aesthetic Surgery, Singapore General Hospital, Singapore, 168751, Singapore. madongrui@yahoo.com.
authors.forename: Dongrui
authors.initials: D
authors.lastname: Ma
authors.affiliation: Skin Bank, Burns Unit, Singapore General Hospital, Singapore, 168751, Singapore. alvin.chua.w.c@sgh.com.sg.
authors.forename: Alvin Wen Choong
authors.initials: AW
authors.lastname: Chua
authors.affiliation: Department of Plastic, Reconstructive & Aesthetic Surgery, Singapore General Hospital, Singapore, 168751, Singapore. ennan_yang@yahoo.com.
authors.forename: Ennan
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Plastic, Reconstructive & Aesthetic Surgery, Singapore General Hospital, Singapore, 168751, Singapore. tpy_fiona@hotmail.com.
authors.forename: Peiyun
authors.initials: P
authors.lastname: Teo
authors.affiliation: Skin Bank, Burns Unit, Singapore General Hospital, Singapore, 168751, Singapore. tinggthinks@gmail.com.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Ting
authors.affiliation: Department of Plastic, Reconstructive & Aesthetic Surgery, Singapore General Hospital, Singapore, 168751, Singapore. colinsong@capeclinic.com.
authors.forename: Colin
authors.initials: C
authors.lastname: Song
authors.affiliation: Institute of Medical Biology, A*STAR, Singapore, 138648, Singapore. birgit.lane@imb.a-star.edu.sg.
authors.forename: Ellen Birgitte
authors.initials: EB
authors.lastname: Lane
authors.affiliation: Department of Plastic, Reconstructive & Aesthetic Surgery, Singapore General Hospital, Singapore, 168751, Singapore. gzzlst@sgh.com.sg.
authors.forename: Seng Teik
authors.initials: ST
authors.lastname: Lee
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000637:transplantation; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D014183:Transplantation, Heterologous
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; C081876:CKAP4 protein, human; D039503:Integrin alpha6; D019012:Integrin beta1; C507540:KRT14 protein, human; D053547:Keratin-14; D008565:Membrane Proteins; D009363:Neoplasm Proteins