title: Increase developmental plasticity of human keratinocytes with gene suppression.
abstract: Recent evidence indicates that p53 suppression increased the efficiency of induced pluripotent stem cell (iPSC) generation. This occurred even with the enforced expression of as few as two canonical transcription factors, Oct4 and Sox2. In this study, primary human keratinocytes were successfully induced into a stage of plasticity by transient inactivation of p53, without enforced expression of any of the transcription factors previously used in iPSC generation. These cells were later redifferentiated into neural lineages. The gene suppression plastic cells were morphologically indistinguishable from human ES cells. Gene suppression plastic cells were alkaline phosphatase-positive, had normal karyotypes, and expressed p53. Together with the accumulating evidence of similarities and overlapping mechanisms between iPSC generation and cancer formation, this finding sheds light on the emerging picture of p53 sitting at the crossroads between two intricate cellular potentials: stem cell vs. cancer cell generation. This finding further supports the crucial role played by p53 in cellular reprogramming and suggests an alternative method to switch the lineage identity of human cells. This reported method offers the potential for directed lineage switching with the goal of generating autologous cell populations for novel clinical applications for neurodegenerative diseases.
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. shengwel@uci.edu
authors.forename: Shengwen Calvin
authors.initials: SC
authors.lastname: Li
authors.forename: Yangsun
authors.initials: Y
authors.lastname: Jin
authors.forename: William G
authors.initials: WG
authors.lastname: Loudon
authors.forename: Yahui
authors.initials: Y
authors.lastname: Song
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ma
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Weiner
authors.forename: Jiang F
authors.initials: JF
authors.lastname: Zhong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007621:Karyotyping; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins