Cell reprogramming. Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming

Science. 2014 Aug 15;345(6198):822-5. doi: 10.1126/science.1254745. Epub 2014 Jul 17.

Abstract

Unfertilized oocytes have the intrinsic capacity to remodel sperm and the nuclei of somatic cells. The discoveries that cells can change their phenotype from differentiated to embryonic state using oocytes or specific transcription factors have been recognized as two major breakthroughs in the biomedical field. Here, we show that ASF1A, a histone-remodeling chaperone specifically enriched in the metaphase II human oocyte, is necessary for reprogramming of human adult dermal fibroblasts (hADFs) into undifferentiated induced pluripotent stem cell. We also show that overexpression of just ASF1A and OCT4 in hADFs exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells. Our Report underscores the importance of studying the unfertilized MII oocyte as a means to understand the molecular pathways governing somatic cell reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Dedifferentiation
  • Cell Differentiation
  • Cellular Reprogramming*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / physiology
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Growth Differentiation Factor 9 / metabolism
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Histones / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Metaphase
  • Molecular Chaperones
  • Octamer Transcription Factor-3 / metabolism
  • Oocytes / cytology
  • Oocytes / physiology
  • Signal Transduction
  • Transcriptional Activation
  • Transcriptome

Substances

  • ASF1A protein, human
  • Cell Cycle Proteins
  • GDF9 protein, human
  • Growth Differentiation Factor 9
  • Histone Chaperones
  • Histones
  • Molecular Chaperones
  • Octamer Transcription Factor-3
  • POU5F1 protein, human