Advanced

Using heterokaryons to understand pluripotency and reprogramming

Piccolo, Francesco M.; Pereira, Carlos F. LU ; Cantone, Irene; Brown, Karen; Tsubouchi, Tomomi; Soza-Ried, Jorge; Merkenschlager, Matthias and Fisher, Amanda G. (2011) In Philosophical Transactions of the Royal Society B: Biological Sciences 366(1575). p.2260-2265
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Cell fusion, Embryonic stem cell, Heterokaryon, Nuclear organization, Pluripotency, Reprogramming
in
Philosophical Transactions of the Royal Society B: Biological Sciences
volume
366
issue
1575
pages
6 pages
publisher
Royal Society
external identifiers
  • scopus:79960073520
ISSN
0962-8436
DOI
10.1098/rstb.2011.0004
language
English
LU publication?
no
id
f84d707c-240d-4d10-9f13-c10a1dd06a24
date added to LUP
2017-10-02 17:29:13
date last changed
2017-10-13 09:57:41
@article{f84d707c-240d-4d10-9f13-c10a1dd06a24,
  abstract     = {<p>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.</p>},
  author       = {Piccolo, Francesco M. and Pereira, Carlos F. and Cantone, Irene and Brown, Karen and Tsubouchi, Tomomi and Soza-Ried, Jorge and Merkenschlager, Matthias and Fisher, Amanda G.},
  issn         = {0962-8436},
  keyword      = {Cell fusion,Embryonic stem cell,Heterokaryon,Nuclear organization,Pluripotency,Reprogramming},
  language     = {eng},
  month        = {07},
  number       = {1575},
  pages        = {2260--2265},
  publisher    = {Royal Society},
  series       = {Philosophical Transactions of the Royal Society B: Biological Sciences},
  title        = {Using heterokaryons to understand pluripotency and reprogramming},
  url          = {http://dx.doi.org/10.1098/rstb.2011.0004},
  volume       = {366},
  year         = {2011},
}