title: Using heterokaryons to understand pluripotency and reprogramming.
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.
authors: Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors: Francesco M
authors: FM
authors: Piccolo
authors: Carlos F
authors: CF
authors: Pereira
authors: Irene
authors: I
authors: Cantone
authors: Karen
authors: K
authors: Brown
authors: Tomomi
authors: T
authors: Tsubouchi
authors: Jorge
authors: J
authors: Soza-Ried
authors: Matthias
authors: M
authors: Merkenschlager
authors: Amanda G
authors: AG
authors: Fisher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D065150:Cellular Reprogramming / Q000502:physiology*; D003584:Cytological Techniques / Q000379:methods; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*