Foxd1 is a mediator and indicator of the cell reprogramming process.
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.
1] RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [3] Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
Makito
M
Koga
1] RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [3] Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
Mitsuhiro
M
Matsuda
1] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [2] Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
Teruhisa
T
Kawamura
1] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [2] Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan.
Takahiro
T
Sogo
1] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [2] Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
Asako
A
Shigeno
1] Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan [2] JST, CREST, Tokyo 102-0075, Japan.
Eisuke
E
Nishida
1] RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [3] JST, CREST, Tokyo 102-0075, Japan.
Miki
M
Ebisuya
D000818:Animals; D065150:Cellular Reprogramming; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse; C467200:Foxo1 protein, mouse