Cyclin D1 acts as a barrier to pluripotent reprogramming by promoting neural progenitor fate commitment

FEBS Lett. 2014 Nov 3;588(21):4008-17. doi: 10.1016/j.febslet.2014.08.039. Epub 2014 Sep 26.

Abstract

A short G1 phase is a characteristic feature of the cell cycle structure of pluripotent cells, and is reestablished during Yamanaka factor-mediated pluripotent reprogramming. How cell cycle control is adjusted to meet the requirements of pluripotent cell fate commitment during reprogramming is less well understood. Elevated levels of cyclin D1 were initially found to impair pluripotency maintenance. The current work further identified Cyclin D1 to be capable of transcriptionally upregulating Pax6, which promoted reprogramming cells to commit to a neural progenitor fate rather than a pluripotent cell fate. These findings explain the importance of reestablishment of G1-phase restriction in pluripotent reprogramming.

Keywords: Cell cycle; Cyclin D; Induced neural stem/progenitor cell; Induced pluripotent stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cellular Reprogramming*
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / metabolism*
  • Eye Proteins / genetics
  • Fibroblasts / cytology
  • G1 Phase
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Humans
  • Mice
  • Nanog Homeobox Protein
  • Neural Stem Cells / cytology*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Repressor Proteins / genetics
  • Transcription, Genetic

Substances

  • Biomarkers
  • Eye Proteins
  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Cyclin D1