MBD3/NuRD Facilitates Induction of Pluripotency in a Context-Dependent Manner

• Published in: Cell stem cell Vol. 15; no. 1; pp. 102 - 110
• Main Authors: dos Santos, Rodrigo L., Tosti, Luca, Radzisheuskaya, Aliaksandra, Caballero, Isabel M., Kaji, Keisuke, Hendrich, Brian, Silva, José C.R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-07-2014; Cell Press
• Subjects: Animals; Cell Dedifferentiation - genetics; Cell Differentiation - genetics; Cell Line; Cellular Reprogramming - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryonic Development - genetics; Gene Knockout Techniques; Homeodomain Proteins - metabolism; Mi-2 Nucleosome Remodeling and Deacetylase Complex - genetics; Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism; Mice; Mice, Inbred Strains; Mice, Knockout; Nanog Homeobox Protein; Neural Stem Cells - physiology; Pluripotent Stem Cells - physiology; Short
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2014.04.019

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.
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•Mbd3 facilitates the initiation of neural stem cell reprogramming•Mbd3 is also required for efficient iPSC generation from EpiSCs and preiPSCs•Overexpression of Mbd3/NuRD facilitates reprogramming in a context-dependent manner
dos Santos et al. show that Mbd3/NuRD plays a positive role in reprogramming in certain contexts and that overexpression of Mbd3 facilitates Nanog-mediated reprogramming.