Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2

Research output: Contribution to journalArticle

Abstract

Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and cell division. Interestingly, reprogramming of human lymphocytes by mouse ES cells elicits the expression of a human ES-specific gene profile, in which markers of human ES cells are expressed (hSSEA4, hFGF receptors and ligands), but markers that are specific to mouse ES cells are not (e.g., Bmp4 and LIF receptor). Using genetically engineered mouse ES cells, we demonstrate that successful reprogramming of human lymphocytes is independent of Sox2, a factor thought to be required for induced pluripotent stem (iPS) cells. In contrast, there is a distinct requirement for Oct4 in the establishment but not the maintenance of the reprogrammed state. Experimental heterokaryons, therefore, offer a powerful approach to trace the contribution of individual factors to the reprogramming of human somatic cells towards a multipotent state.

Details

Authors
  • Carlos F. Pereira
  • Rémi Terranova
  • Natalie K. Ryan
  • Joana Santos
  • Kelly J. Morris
  • Wei Cui
  • Matthias Merkenschlager
  • Amanda G. Fisher
External organisations
  • Hammersmith Hospital
Original languageEnglish
Article numbere1000170
JournalPLoS Genetics
Volume4
Issue number9
Publication statusPublished - 2008 Sep
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes