MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner.
The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for embryonic development and pluripotent stem cell differentiation. In this study, we investigated whether NuRD is also involved in the reverse biological process of induction of pluripotency in neural stem cells. By knocking out MBD3, an essential scaffold subunit of the NuRD complex, at different time points in reprogramming, we found that efficient formation of reprogramming intermediates and induced pluripotent stem cells from neural stem cells requires NuRD activity. We also show that reprogramming of epiblast-derived stem cells to naive pluripotency requires NuRD complex function and that increased MBD3/NuRD levels can enhance reprogramming efficiency when coexpressed with the reprogramming factor NANOG. Our results therefore show that the MBD3/NuRD complex plays a key role in reprogramming in certain contexts and that a chromatin complex required for cell differentiation can also promote reversion back to a naive pluripotent cell state.
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Doctoral Programme in Experimental Biology and Biomedicine, Centre for Neuroscience and Cell Biology and Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
Rodrigo L
RL
dos Santos
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh BioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Luca
L
Tosti
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Aliaksandra
A
Radzisheuskaya
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh BioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Isabel M
IM
Caballero
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh BioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Keisuke
K
Kaji
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Brian
B
Hendrich
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. Electronic address: jcs64@cscr.cam.ac.uk.
José C R
JC
Silva
D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D055786:Gene Knockout Techniques; D018398:Homeodomain Proteins / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D058953:Neural Stem Cells / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000502:physiology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C115369:MBD3 protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex