title: Induction of pluripotency in mouse somatic cells with lineage specifiers.
abstract: The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendodermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a "seesaw model" in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.
authors.affiliation: MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shu
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Yetao
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Sida
authors.initials: S
authors.lastname: Shao
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Lijun
authors.initials: L
authors.lastname: Shen
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Zuo
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chi
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.forename: Youmin
authors.initials: Y
authors.lastname: Shu
authors.forename: Kehu
authors.initials: K
authors.lastname: Yuan
authors.forename: Weiwu
authors.initials: W
authors.lastname: He
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D013270:Stomach / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C088334:Distal-less homeobox proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors