title: Reprogramming sertoli cells into pluripotent stem cells.
abstract: Induced pluripotent stem cells (iPSCs) have potential applications in the restoration of fertility, regenerative medicine, and animal biotechnology. In this study, we present the induction of iPSCs from mouse Sertoli cells (SCs) by introducing four factors--Oct4, Sox2, Klf4, and c-Myc. As early as day 3 after induction, expression of these factors was detected and typical embryonic stem-like cells began to form. On day 18, these exogenous genes were silenced and colonies were selected according to morphological characteristics. The iPSCs induced from SCs, termed SCiPSCs, strongly expressed pluripotent markers, showed a normal karyotype, and had proliferation and differentiation characteristics similar to those of embryonic stem cells (ESCs), both in vitro and in vivo. Furthermore, exposure of SCiPSCs to nitric oxide (NO) allowed them to maintain pluripotency through the activation of the pluripotent genes Oct4 and Sox2 and upregulation of Nanog expression. Moreover, NO prevented SCiPSCs from undergoing apoptosis by activating the antiapoptotic genes Bcl2 and Bcl2lll, downregulating the proapoptotic genes Bak1 and Casp7, and blocking the activation of the proapoptotic gene Bac. These effects were reversed by exposure to l-NG-monomethylarginine (l-NMMA), a NO inhibitor. These data demonstrate that iPSCs can be generated from SCs and that the self-renewal and pluripotency of SCiPS cells can be maintained in the presence of NO.
authors.affiliation: 1 Transgenic and Stem Cell Core, National Institute of Animal Science and Veterinary Medicine , Chinese Academy of Agricultural Sciences, Beijing, China .
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sun
authors.forename: Guomin
authors.initials: G
authors.lastname: Zhang
authors.forename: Fulu
authors.initials: F
authors.lastname: Dong
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Wenguang
authors.initials: W
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D065150:Cellular Reprogramming; D017931:DNA Primers; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D000090062:Kruppel-Like Factor 4; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012708:Sertoli Cells / Q000166:cytology*
chemical_list: D017931:DNA Primers; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D009569:Nitric Oxide