Int J Stem Cells.  2018 Nov;11(2):235-241. 10.15283/ijsc18036.

Mbd3 Promotes Reprogramming of Primary Human Fibroblasts

Affiliations
  • 1Department of Haematology, University College London, Cancer Institute, London, UK. amit.nathwani@ucl.ac.uk
  • 2Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free NHS Trust, London, UK.
  • 3National Health Services Blood and Transplant, Oak House, Reeds Crescent, Watford, Hertfordshire, UK.
  • 4Centre for Paediatrics, Barts and The London Medical School, Blizard Institute, Queen Mary University of London, London, UK.

Abstract

Mbd3 (Methyl-CpG binding domain protein), a core member of NuRD (nucleosome remodelling and deacetylation) is essential for embryogenesis. However, its role in reprogramming of somatic cells into induced pluripotent stem cells (iPSC) remains controversial. Some reports suggest that Mbd3 inhibits pluripotency, whilst others show that it greatly enhances reprogramming efficiency. Our study is the first to assess the role of Mbd3 on reprogramming of primary human fibroblasts using Yamanaka episomal plasmids (Reprogramming factors (RF) under feeder-free conditions. We showed that shRNA-mediated partial depletion of Mbd3 resulted in >5-fold reduction in the efficiency of reprogramming of primary human fibroblasts. Furthermore, iPSC that emerged after knock-down of Mbd3 were incapable of trilineage differentiation even though they expressed all markers of pluripotency. In contrast, over-expression of the Mbd3b isoform along with the Yamanaka episomal plasmids increased the number of fibroblast derived iPSC colonies by at least two-fold. The resulting colonies were capable of trilineage differentiation. Our results, therefore, suggest that Mbd3 appears to play an important role in reprogramming of primary human fibroblasts, which provides further insight into the biology of reprogramming but also has direct implication for translation of iPSC to clinic.

Keyword

Mbd3; Induced pluripotent stem cells; Episomal reprogramming; Fibroblasts

MeSH Terms

Biology
Embryonic Development
Female
Fibroblasts*
Humans*
Induced Pluripotent Stem Cells
Plasmids
Pregnancy
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