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Foxd1 is a mediator and indicator of the cell reprogramming process
Makito Koga1, Mitsuhiro Matsuda1, Teruhisa Kawamura2
11] 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.
Nature Communications
|February 6, 2014
Summary
Two transcription factors, Foxd1 and Foxo1, mediate gene expression changes during cell reprogramming. Foxd1 acts as both a mediator and indicator of successful induced pluripotent stem cell (iPSC) generation.
Area of Science:
- * Molecular Biology
- * Developmental Biology
- * Stem Cell Biology
Background:
- * The precise mechanisms driving gene expression changes during cell reprogramming to a pluripotent state are not fully understood.
- * Identifying key regulators is crucial for improving reprogramming efficiency and understanding pluripotency maintenance.
Purpose of the Study:
- * To identify transcription factors involved in mediating gene expression changes during cell reprogramming.
- * To elucidate the role of Foxd1 and Foxo1 in the generation of induced pluripotent stem cells (iPSCs).
Main Methods:
- * Gene knockdown experiments targeting Foxd1 and Foxo1.
- * Gene knockout studies for Foxd1.
- * Analysis of downstream transcriptional events, including Dax1 expression.
- * Fate mapping analyses to trace the origin of iPSC colonies.
Main Results:
- * Knockdown of Foxd1 or Foxo1 significantly reduced the number of generated iPSCs.
- * Double knockdown of Foxd1 and Foxo1 further diminished iPSC formation.
- * Foxd1 knockout impaired downstream transcriptional events, such as Dax1 expression, essential for pluripotency.
- * Transient upregulation of Foxd1 was observed in cells progressing towards an iPSC fate.
- * Fate mapping confirmed that over 95% of iPSC colonies originated from Foxd1-positive cells.
Conclusions:
- * Foxd1 and Foxo1 are critical mediators of gene expression reprogramming.
- * Foxd1 functions as both a key mediator and a reliable indicator of successful reprogramming to pluripotency.
- * Foxd1's transient expression marks cells committed to an iPSC fate.
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