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

Pereira, Carlos F. LU ; Terranova, Rémi; Ryan, Natalie K.; Santos, Joana; Morris, Kelly J.; Cui, Wei; Merkenschlager, Matthias and Fisher, Amanda G. (2008) In PLoS Genetics 4(9).
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... (More)

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.

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author
publishing date
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publication status
published
in
PLoS Genetics
volume
4
issue
9
publisher
Public Library of Science
external identifiers
  • scopus:52949106486
ISSN
1553-7390
DOI
10.1371/journal.pgen.1000170
language
English
LU publication?
no
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b3379cce-df25-4802-94ce-4cc9bba990c3
date added to LUP
2017-10-02 17:33:52
date last changed
2017-10-13 08:32:18
@article{b3379cce-df25-4802-94ce-4cc9bba990c3,
  abstract     = {<p>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.</p>},
  articleno    = {e1000170},
  author       = {Pereira, Carlos F. and Terranova, Rémi and Ryan, Natalie K. and Santos, Joana and Morris, Kelly J. and Cui, Wei and Merkenschlager, Matthias and Fisher, Amanda G.},
  issn         = {1553-7390},
  language     = {eng},
  number       = {9},
  publisher    = {Public Library of Science},
  series       = {PLoS Genetics},
  title        = {Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1000170},
  volume       = {4},
  year         = {2008},
}