Side population keratinocytes resembling bone marrow side population stem cells are distinct from label-retaining keratinocyte stem cells.
Very primitive hematopoietic stem cells have been identified as side population cells based on their ability to efflux a fluorescent vital dye, Hoechst 33342. In this study we show that keratinocytes with the same side population phenotype are also present in the human epidermis. Although side population keratinocytes have the same dye-effluxing phenotype as bone marrow side population cells and can be blocked by verapamil, they do not express increased levels of the ABCG2 transporter that is believed to be responsible for the bone marrow side population phenotype. Because bone marrow side population cells have stem cell characteristics, we sought to determine if side population keratinocytes represent a keratinocyte stem cell population by comparing side population keratinocytes with a traditional keratinocyte stem cell candidate, label-retaining keratinocytes. Flow cytometric analyses demonstrated that side population keratinocytes have a different cell surface phenotype (low beta1 integrin and low alpha6 integrin expression) than label-retaining keratinocytes and represent a unique population of keratinocytes distinctly different from the traditional keratinocyte stem cell candidate. Future in vivo studies will be required to analyze the function of side population keratinocytes in epidermal homeostasis and to determine if side population keratinocytes have characteristics of keratinocyte stem cells.
Terunuma
Atsushi
A
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1908, USA.
Jackson
Kimberly L
KL
Kapoor
Veena
V
Telford
William G
WG
Vogel
Jonathan C
JC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002478:Cells, Cultured; D000078404:Epidermal Cells; D016193:G1 Phase; D006801:Humans; D039503:Integrin alpha6 / Q000032:analysis; D019012:Integrin beta1 / Q000032:analysis; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D016038:Skin Transplantation; D013234:Stem Cells / Q000166:cytology*
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D039503:Integrin alpha6; D019012:Integrin beta1; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D001973:Bromodeoxyuridine