Cell cycle dynamics in the reprogramming of cellular identity

FEBS Lett. 2019 Oct;593(20):2840-2852. doi: 10.1002/1873-3468.13625. Epub 2019 Oct 9.

Abstract

Reprogramming of cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multidimensional epigenomic changes, whereas genome replication demands fidelity. In this review, we discuss how the pace of the genome's replication and cell cycle influences the way daughter cells take on their identity. We highlight several biochemical processes that are pertinent to cell fate control, whose propagation into the daughter cells should be governed by more complex mechanisms than simple templated replication. With this mindset, we summarize multiple scenarios where rapid cell cycle could interfere with cell fate copying and promote cell fate reprogramming. Prominent examples of cell fate regulation by specific cell cycle phases are also discussed. Overall, there is much to be learned regarding the relationship between cell fate reprogramming and cell cycle control. Harnessing cell cycle dynamics could greatly facilitate the derivation of desired cell types.

Keywords: cell cycle speed; cell fate; hematopoietic progenitors; pluripotent stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / genetics*
  • Cell Differentiation
  • Cell Lineage / genetics*
  • Cellular Reprogramming / genetics*
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Epigenesis, Genetic*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Organ Specificity

Substances

  • Chromatin
  • Histones
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Cyclin-Dependent Kinases