title: Loss of Pten causes tumor initiation following differentiation of murine pluripotent stem cells due to failed repression of Nanog.
abstract: Pluripotent stem cells (PSCs) hold significant promise in regenerative medicine due to their unlimited capacity for self-renewal and potential to differentiate into every cell type in the body. One major barrier to the use of PSCs is their potential risk for tumor initiation following differentiation and transplantation in vivo. In the current study we sought to evaluate the role of the tumor suppressor Pten in murine PSC neoplastic progression. Using eight functional assays that have previously been used to indicate PSC adaptation or transformation, Pten null embryonic stem cells (ESCs) failed to rate as significant in five of them. Instead, our data demonstrate that the loss of Pten causes the emergence of a small number of aggressive, teratoma-initiating embryonic carcinoma cells (ECCs) during differentiation in vitro, while the remaining 90-95% of differentiated cells are non-tumorigenic. Furthermore, our data show that the mechanism by which Pten null ECCs emerge in vitro and cause tumors in vivo is through increased survival and self-renewal, due to failed repression of the transcription factor Nanog.
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Lindgren
authors.forename: Kyle
authors.initials: K
authors.lastname: Natsuhara
authors.forename: E
authors.initials: E
authors.lastname: Tian
authors.forename: John J
authors.initials: JJ
authors.lastname: Vincent
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Jiao
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Utpal
authors.initials: U
authors.lastname: Banerjee
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D053595:Embryonic Stem Cells; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D039904:Pluripotent Stem Cells / Q000473:pathology*
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse