title: Wnt/β-catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro.
abstract: Aged epidermal cells have the capacity to dedifferentiate into stem cell-like cells. However, the signals that regulate the dedifferentiation of aged epidermal cells remain unclear. Here, we provide evidence that Wnt/β-catenin is critical for aged epidermal cell dedifferentiation in vivo and in vitro. Some aged epidermal cells in human ultrathin epidermal sheets lacking basal stem cells transplanted onto wounds dedifferentiated into stem cell-like cells that were positive for CK19 and β1 integrin but negative for CK10. In addition, Wnt/β-catenin pathway was activated during this process. There was increased expression of Wnt-1, Wnt-4, Wnt-7a, β-catenin, cyclin D1, and c-myc. Secreted frizzled-related protein 1, a Wnt/β-catenin pathway inhibitor, blocked dedifferentiation in vivo. Then, the activator, a highly specific glycogen synthase kinase (GSK)-3β inhibitor, of Wnt/β-catenin pathway was added to the culture medium of aged epidermal cells. Surprisingly, we found that the activator induced higher expression of CK19, β1 integrin, Oct4, and Nanog proteins. The induced aged epidermal cells exhibited high colony-forming efficiency, long-term proliferative potential and could regenerate a skin equivalent (as do epidermal stem cells). These results suggested that activation of Wnt/β-catenin pathway induced the dedifferentiation of aged epidermal cells, which suggest a new approach to generate epidermal stem cell-like cells.
authors.affiliation: Wound Healing and Cell Biology Laboratory, Burns Institute, The First Affiliated Hospital, General Hospital of PLA, Beijing, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Fei
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zhao
authors.forename: Tongzhu
authors.initials: T
authors.lastname: Sun
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Sheng
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016038:Skin Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000099274:Frizzled-Related Proteins
chemical_list: D015415:Biomarkers; D019938:Cyclin D1; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C489427:MYC protein, human