title: Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency.
abstract: Nanog expression is heterogeneous and dynamic in embryonic stem cells (ESCs). However, the mechanism for stabilizing pluripotency during the transitions between Nanog(high) and Nanog(low) states is not well understood. Here we report that Dax1 acts in parallel with Nanog to regulate mouse ESC (mESCs) identity. Dax1 stable knockdown mESCs are predisposed towards differentiation but do not lose pluripotency, whereas Dax1 overexpression supports LIF-independent self-renewal. Although partially complementary, Dax1 and Nanog function independently and cannot replace one another. They are both required for full reprogramming to induce pluripotency. Importantly, Dax1 is indispensable for self-renewal of Nanog(low) mESCs. Moreover, we report that Dax1 prevents extra-embryonic endoderm (ExEn) commitment by directly repressing Gata6 transcription. Dax1 may also mediate inhibition of trophectoderm differentiation independent or as a downstream effector of Oct4. These findings establish a basal role of Dax1 in maintaining pluripotency during the state transition of mESCs and somatic cell reprogramming.
authors.affiliation: Department of Microbiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Junlei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gaoke
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 400038, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing 100071, China [2] Department of Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 400038, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Hongting
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Research Center of Laboratory Medicine, Chengdu Military General Hospital, Sichuan 610083, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Microbiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Hu
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jian
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D057137:DAX-1 Orphan Nuclear Receptor / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology*; D050993:GATA6 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C539966:Nr0b1 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D034741:RNA, Small Interfering