Esrrb Is a Direct Nanog Target Gene that Can Substitute for Nanog Function in Pluripotent Cells

被引：260

作者：

Festuccia, Nicola ^{[1
]}

Osorno, Rodrigo ^{[1
]}

Halbritter, Florian ^{[1
]}

Karwacki-Neisius, Violetta ^{[1
]}

Navarro, Pablo ^{[1
]}

Colby, Douglas ^{[1
]}

Wong, Frederick ^{[1
]}

Yates, Adam ^{[1
]}

Tomlinson, Simon R. ^{[1
]}

Chambers, Ian ^{[1
]}

机构：

[1] Univ Edinburgh, MRC Ctr Regenerat Med, Inst Stem Cell Res, Sch Biol Sci, Edinburgh EH16 4UU, Midlothian, Scotland

来源：

CELL STEM CELL | 2012年 / 11卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

TRANSCRIPTIONAL REGULATORY CIRCUITRY; PROTEIN-INTERACTION NETWORK; STEM-CELLS; GROUND-STATE; SELF-RENEWAL; MOUSE EPIBLAST; SIGNALING PATHWAYS; OCT4; EXPRESSION; HETEROGENEITY;

D O I：

10.1016/j.stem.2012.08.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Embryonic stem cell (ESC) self-renewal efficiency is determined by the level of Nanog expression. However, the mechanisms by which Nanog functions remain unclear, and in particular, direct Nanog target genes are uncharacterized. Here we investigate ESCs expressing different Nanog levels and Nanog(-/-) cells with distinct functionally inducible Nanog proteins to identify Nanog-responsive genes. Surprisingly, these constitute a minor fraction of genes that Nanog binds. Prominent among Nanog-reponsive genes is Estrogen-related receptor b (Esrrb). Nanog binds directly to Esrrb, enhances binding of RNAPoIII, and stimulates Esrrb transcription. Overexpression of Esrrb in ESCs maintains cytokine-independent self-renewal and pluripotency. Remarkably, this activity is retained in Nanog(-/-) ESCs. Moreover, Esrrb can reprogram Nanog(-/-) EpiSCs and can rescue stalled reprogramming in Nanog(-/-) pre-iPSCs. Finally, Esrrb deletion abolishes the defining ability of Nanog to confer LIE-independent ESC selfrenewal. These findings are consistent with the functional placement of Esrrb downstream of Nanog.

引用

页码：477 / 490

页数：14

共 48 条

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