title: Overexpression of cyclin D1 induces the reprogramming of differentiated epidermal cells into stem cell-like cells.
abstract: It has been reported that Wnt/β-catenin is critical for dedifferentiation of differentiated epidermal cells. Cyclin D1 (CCND1) is a β-catenin target gene. In this study, we provide evidence that overexpression of CCND1 induces reprogramming of epidermal cells into stem cell-like cells. After introducing CCND1 gene into differentiated epidermal cells, we found that the large flat-shaped cells with a small nuclear-cytoplasmic ratio changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. The expressions of CK10, β1-integrin, Oct4 and Nanog in CCND1 induced cells were remarkably higher than those in the control group (P < 0.01). In addition, the induced cells exhibited a high colony-forming ability and a long-term proliferative potential. When the induced cells were implanted into a wound of laboratory animal model, the wound healing was accelerated. These results suggested that overexpression of CCND1 induced the reprogramming of differentiated epidermal cells into stem cell-like cells. This study may also offer a new approach to yield epidermal stem cells for wound repair and regeneration.
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.|b Tianjin Medical University , Tianjin , PR China.
authors.forename: Along
authors.initials: A
authors.lastname: Zhao
authors.affiliation: c Institute of Radiation Medicine, Academy of Military Medical Sciences , Beijing , P.R. China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Yang
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.
authors.forename: Mengli
authors.initials: M
authors.lastname: Sun
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: c Institute of Radiation Medicine, Academy of Military Medical Sciences , Beijing , P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: d Burn and Plastic Surgery, The Second Affiliated Hospital, Shantou University Medical College , Shantou , Guangdong Province , P.R. China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.affiliation: a Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D048430:Cell Shape; D065150:Cellular Reprogramming; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D019012:Integrin beta1 / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D009368:Neoplasm Transplantation; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D014945:Wound Healing
chemical_list: C530104:CCND1 protein, human; D019012:Integrin beta1; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D019938:Cyclin D1; D007633:Keratins
keywords: Cyclin D1; dedifferentiation; epidermal stem cells; reprogramming; wound repair