Corneal epithelial-like transdifferentiation of hair follicle stem cells is mediated by pax6 and beta-catenin/Lef-1.
Several types of adult stem cells are capable of transdifferentiaton into other types of tissues. The hair follicle bulge area is an abundant and easily accessible source of pluripotent adult stem cells. We demonstrate that the bulge KSCs have the potential for transdifferentiation into corneal epithelial-like cells. Bulge KSCs isolated by collagen type IV adhesiveness possessed the highest colony formation efficiency (CFE), and expressed specific markers (CD34 and alpha6-integrin). The isolated cells transdifferentiate into corneal epithelial-like cells in conditioned medium containing corneal limbus soluble factors, including their specific marker, keratin12. The transdifferentiation depends on upregulation of pax6 and downregulation of beta-catenin and Lef-1. Furthermore, overexpression of pax6 in bulge KSCs induced their expression of k12. The expressions of beta-catenin and Lef-1 were not suppressed in the pax6-transfected bulge KSCs, but which were downregulated pax6-transfected cells cultured in the conditioned medium. Bulge KSCs may have potential therapeutic application as cell source for the construction of bioengineered corneas.
Yang
Ke
K
Department of Cell Biology, Third Military Medical University, Gaotanyan, Chongqing 400038, PR China.
Jiang
Zilin
Z
Wang
Dong
D
Lian
Xiaohua
X
Yang
Tian
T
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D054338:Cell Transdifferentiation; D019573:Epithelium, Corneal / Q000166:cytology*; D005136:Eye Proteins / Q000378:metabolism*; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D039503:Integrin alpha6 / Q000378:metabolism; D053551:Keratin-12 / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D018952:Antigens, CD34; D005136:Eye Proteins; D018398:Homeodomain Proteins; D039503:Integrin alpha6; D053551:Keratin-12; D051821:Lymphoid Enhancer-Binding Factor 1; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D051176:beta Catenin