title: Direct reprogramming of human fibroblasts into sweat gland-like cells.
abstract: The skin of patients with an extensive deep burn injury is repaired by a process that leaves a hypertrophic scar without sweat glands and therefore loses the function of perspiration. The aim of this study was to identify whether the key factors related to sweat gland development could directly reprogram fibroblasts into sweat gland-like cells. After introducing the NF-κB and Lef-1 genes into fibroblasts, we found that stably transfected fibroblasts expressed specific markers of sweat glands, including CEA, CK7, CK14 and CK19, both at the protein and mRNA levels. The immunofluorescence staining also showed positive expression of CEA, CK7, CK14 and CK19 in induced fibroblasts, but there were no positive cells in the control groups. The expression of Shh and Cyclin D1, downstream genes of NF-κB and Lef-1, were also significantly increased during regeneration. The induced fibroblasts were implanted into an animal model. Twenty days later, iodine-starch perspiration tests showed that 7 out of the 10 cell-treated paws were positive for perspiration, with a distinctive black point-like area appearing in the center of the paw. Contralateral paws tested negative. Histological examination of skin biopsies from experimental and control paws revealed that sweat glands were fully reconstructed in the test paws, with integral, secretory and ductal portions, but were not present in the control paws. This is the first report of successful reprogramming of fibroblasts into sweat gland-like cells, which will provide a new cell source for sweat gland regeneration in patients with extensive deep burns.
authors.affiliation: a Would Healing and Cell Biology Laboratory; Institute of Basic Medical Science; General Hospital of PLA ; Beijing , China.|b Department of Plastic Surgery ; General Hospital of The Second Artillery Corps ; Beijing , China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: c Department of Gynecology and Obstetrics ; General Hospital of Shenyang Military Region ; Shenyang , China.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Xu
authors.affiliation: d Department of Plastic Surgery ; General Hospital of PLA ; Beijing , China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: e Key Laboratory of Wound Repair and Regeneration of PLA; The first affiliated hospital; General Hospital of PLA ; Beijing , China.
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.affiliation: e Key Laboratory of Wound Repair and Regeneration of PLA; The first affiliated hospital; General Hospital of PLA ; Beijing , China.
authors.forename: Mengli
authors.initials: M
authors.lastname: Sun
authors.affiliation: b Department of Plastic Surgery ; General Hospital of The Second Artillery Corps ; Beijing , China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Tian
authors.affiliation: e Key Laboratory of Wound Repair and Regeneration of PLA; The first affiliated hospital; General Hospital of PLA ; Beijing , China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: e Key Laboratory of Wound Repair and Regeneration of PLA; The first affiliated hospital; General Hospital of PLA ; Beijing , China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D006085:Graft Survival; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013545:Sweat Glands / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D013546:Sweating; D013997:Time Factors; D014162:Transfection
chemical_list: C530104:CCND1 protein, human; D002272:Carcinoembryonic Antigen; D005819:Genetic Markers; D053823:Hedgehog Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D016328:NF-kappa B; D012333:RNA, Messenger; C509239:SHH protein, human; D019938:Cyclin D1; D007633:Keratins
keywords: Lef-1; NF-κB; fibroblast; regeneration; reprogramming; sweat glands