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

Title: Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2
Authors: Pereira, CF
Terranova, R
Ryan, NK
Santos, J
Morris, KJ
Cui, W
Merkenschlager, M
Fisher, AG
Item Type: Journal Article
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 ESspecific 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.
Issue Date: 1-Sep-2008
Date of Acceptance: 15-Jul-2008
URI: http://hdl.handle.net/10044/1/71581
DOI: https://doi.org/10.1371/journal.pgen.1000170
ISSN: 1553-7390
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS Genetics
Volume: 4
Issue: 9
Copyright Statement: © 2008 Pereira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: PO4050659629
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
EMBRYONIC STEM-CELLS
NUCLEAR TRANSFER
SOMATIC-CELLS
MATURE B
EXPRESSION
NANOG
FIBROBLASTS
TRANSCRIPTION
FUSION
DIFFERENTIATION
Animals
B-Lymphocytes
Cell Differentiation
Cell Fusion
Cell Nucleus
Cellular Reprogramming
DNA-Binding Proteins
Embryonic Stem Cells
HMGB Proteins
Homeodomain Proteins
Humans
Hybrid Cells
Mice
Nanog Homeobox Protein
Octamer Transcription Factor-3
Pluripotent Stem Cells
SOXB1 Transcription Factors
Transcription Factors
B-Lymphocytes
Hybrid Cells
Cell Nucleus
Pluripotent Stem Cells
Animals
Humans
Mice
DNA-Binding Proteins
HMGB Proteins
Homeodomain Proteins
Transcription Factors
Cell Fusion
Cell Differentiation
Octamer Transcription Factor-3
Embryonic Stem Cells
SOXB1 Transcription Factors
Cellular Reprogramming
Nanog Homeobox Protein
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
EMBRYONIC STEM-CELLS
NUCLEAR TRANSFER
SOMATIC-CELLS
MATURE B
EXPRESSION
NANOG
FIBROBLASTS
TRANSCRIPTION
FUSION
DIFFERENTIATION
Developmental Biology
0604 Genetics
Publication Status: Published
Article Number: e1000170
Online Publication Date: 2008-09-05
Appears in Collections:Division of Surgery
Clinical Sciences
Molecular Sciences
Faculty of Medicine



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