Foxd1 is a mediator and indicator of the cell reprogramming process

被引：63

作者：

Koga, Makito ^{[1
,2
,3
]}

Matsuda, Mitsuhiro ^{[1
,2
,3
]}

Kawamura, Teruhisa ^{[2
,4
]}

Sogo, Takahiro ^{[2
,5
]}

Shigeno, Asako ^{[2
,4
]}

Nishida, Eisuke ^{[3
,6
]}

Ebisuya, Miki ^{[1
,2
,6
]}

机构：

[1] RIKEN Ctr Dev Biol, Kobe, Hyogo 6500047, Japan

[2] Kyoto Univ, Career Path Promot Unit Young Life Sci, Kyoto 6068501, Japan

[3] Kyoto Univ, Grad Sch Biostudies, Kyoto 6068502, Japan

[4] Ritsumeikan Univ, Coll Life Sci, Dept Biomed Sci, Shiga 5258577, Japan

[5] Natl Hosp Org, Kyoto Med Ctr, Div Translat Res, Kyoto 6128555, Japan

[6] CREST, JST, Tokyo 1020075, Japan

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

PLURIPOTENT STEM-CELLS; EXPRESSION CLONING; MOUSE; FIBROBLASTS; GENERATION; INDUCTION; SITES; NANOG; MYC;

D O I：

10.1038/ncomms4197

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

It remains unclear how changes in gene expression profiles that establish a pluripotent state are induced during cell reprogramming. Here we identify two forkhead box transcription factors, Foxd1 and Foxo1, as mediators of gene expression programme changes during reprogramming. Knockdown of Foxd1 or Foxo1 reduces the number of iPSCs, and the double knockdown further reduces it. Knockout of Foxd1 inhibits downstream transcriptional events, including the expression of Dax1, a component of the autoregulatory network for maintaining pluripotency. Interestingly, the expression level of Foxd1 is transiently increased in a small population of cells in the middle stage of reprogramming. The transient Foxd1 upregulation in this stage is correlated with a future cell fate as iPSCs. Fate mapping analyses further reveal that >95% of iPSC colonies are derived from the Foxd1-positive cells. Thus, Foxd1 is a mediator and indicator of successful progression of reprogramming.

引用

页数：9

共 42 条

[1] Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase [J].