Using heterokaryons to understand pluripotency and reprogramming

Research output: Contribution to journalArticle

Abstract

Reprogramming differentiated cells towards pluripotency can be achieved by different experimental strategies including the forced expression of specific 'inducers' and nuclear transfer. While these offer unparalleled opportunities to generate stem cells and advance disease modelling, the relatively low levels of successful reprogramming achieved (1-2%) makes a direct analysis of the molecular events associated with productive reprogramming very challenging. The generation of transient heterokaryons between human differentiated cells (such as lymphocytes or fibroblasts) and mouse pluripotent stem cell lines results in a much higher frequency of successful conversion (15% SSEA4 expressing cells) and provides an alternative approach to study early events during reprogramming. Under these conditions, differentiated nuclei undergo a series of remodelling events before initiating human pluripotent gene expression and silencing differentiation-associated genes. When combined with genetic or RNAi-based approaches and high-throughput screens, heterokaryon studies can provide important new insights into the factors and mechanisms required to reprogramme unipotent cells towards pluripotency.

Details

Authors
  • Francesco M. Piccolo
  • Carlos F. Pereira
  • Irene Cantone
  • Karen Brown
  • Tomomi Tsubouchi
  • Jorge Soza-Ried
  • Matthias Merkenschlager
  • Amanda G. Fisher
External organisations
  • Hammersmith Hospital
  • Lymphocyte Development Group, London Institue of Medical Sciences
  • Icahn School of Medicine at Mount Sinai
  • University of Sussex
Research areas and keywords

Keywords

  • Cell fusion, Embryonic stem cell, Heterokaryon, Nuclear organization, Pluripotency, Reprogramming
Original languageEnglish
Pages (from-to)2260-2265
Number of pages6
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume366
Issue number1575
Publication statusPublished - 2011 Jul 4
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes