title: Vitamin C promotes pluripotency of human induced pluripotent stem cells via the histone demethylase JARID1A.
abstract: Somatic cells can be reprogramed into induced pluripotent stem (iPS) cells by defined factors, which provide a powerful basis for personalized stem-cell based therapies. However, cellular reprograming is an inefficient and metabolically demanding process commonly associated with obstacles that hamper further use of this technology. Spontaneous differentiation of iPS cells cultures represents a significant hurdle that hinder obtaining high quality iPS cells for further downstream experimentation. In this study, we found that a natural compound, vitamin C, augmented pluripotency in iPS cells and reduced unwanted spontaneous differentiation during iPS cells maintenance. Gene expression analysis showed that vitamin C increased the expression of the histone demethylase JARID1A. Furthermore, through gain- and loss-of-function approaches, we show that JARID1A is a key effector in promoting pluripotency and reducing differentiation downstream of vitamin C. Our results therefore highlight a straightforward method for improving the pluripotency and quality of iPS cells; it also shows a possible role for H3K4me2/3 in cell fate determination and establishes a link between vitamin C and epigenetic regulation.
authors.forename: Wassim
authors.initials: W
authors.lastname: Eid
authors.forename: Wafaa
authors.initials: W
authors.lastname: Abdel-Rehim
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D056485:Retinoblastoma-Binding Protein 2 / Q000378:metabolism*
chemical_list: D006657:Histones; C070050:KDM5A protein, human; D056485:Retinoblastoma-Binding Protein 2; D001205:Ascorbic Acid