Side population in adult murine epidermis exhibits phenotypic and functional characteristics of keratinocyte stem cells.
Based on functional studies in the bone marrow, it has been suggested that the ability to efflux Hoechst 33342 may represent a universal stem cell trait. In this phenotypic and functional characterization of the Hoechst side population (SP) in adult murine epidermis, we demonstrate that these cells are a rare subset of the keratinocyte stem cell-enriched alpha(6)(bri)CD71(dim) fraction comprising SSC(low)/K14(+)/CD34(-)/Oil red O(-)/c-kit(-)/CD45(-) keratinocytes. Epidermal SPs have the smallest cell and nuclear size but exhibit the highest nuclear-to-cytoplasmic ratio of any fraction examined, consistent with a primitive cell type. Although SPs demonstrated poor cumulative in vitro proliferative output, they exhibited sustained epidermal tissue-regenerative activity in vivo compared with unfractionated and non-SP cells. Collectively, these results indicate that the epidermal SP contains the most potent keratinocyte stem cell population in skin epithelium.
Redvers
Richard P
RP
Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Trescowthick Research Laboratories, St. Andrew's Place, East Melbourne, Victoria 3002, Australia.
Li
Amy
A
Kaur
Pritinder
P
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D000078404:Epidermal Cells; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D013623:Tail / Q000166:cytology; D014132:Trachea / Q000166:cytology
D015703:Antigens, CD; C068126:CD71 antigen; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D011990:Receptors, Transferrin