Neurotrophin receptor p75(NTR) characterizes human esophageal keratinocyte stem cells in vitro.
We report here that human esophageal keratinocyte stem cells are characterized by the expression of the low-affinity neurotrophin receptor p75(NTR) and differentially expressed cell adhesion molecules, the beta1 and beta4 integrins. The candidate stem cells could be fractionated from keratinocytes as a minor cell subset by means of immunocytochemical cell sorting based on the different levels of expression of these cell surface molecules. Flow cytometric analysis revealed that this minor cell subset retained a relatively slow-cycling phenotype in vitro. These cells expressed low levels of involucrin and cytokeratin 13, indicating that the p75(NTR)-positive cell subset is immature relative to the other predominant subpopulations coexpressing beta1 integrin at higher levels. The p75(NTR)-positive cell subset was crucial for achieving longevity and the greatest output of keratinocytes comprising all distinguishable subpopulations in vitro. This process was associated with self-renewal and self-amplification of the p75(NTR)-positive cell subset. These findings strongly implicate p75(NTR) as a stem cell marker, which will be valuable for prospectively investigating stem cell regulation in association with different biological processes including neoplastic transformation of regenerative epithelia.
Okumura
Tomoyuki
T
Laboratory of Molecular Cell Biology and Oncology, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
Shimada
Yutaka
Y
Imamura
Masayuki
M
Yasumoto
Shigeru
S
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000378:metabolism; D004947:Esophagus / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism; D039663:Integrin beta4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010641:Phenotype; D011419:Propidium / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D019012:Integrin beta1; D039663:Integrin beta4; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D011419:Propidium; C032253:involucrin; D007633:Keratins