Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all–iPS cell mice from terminally differentiated B cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-04

AUTHORS

Matthias Stadtfeld, Effie Apostolou, Francesco Ferrari, Jiho Choi, Ryan M Walsh, Taiping Chen, Steen S K Ooi, Sang Yong Kim, Timothy H Bestor, Toshi Shioda, Peter J Park, Konrad Hochedlinger

ABSTRACT

The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster, compromising the ability to generate entirely iPSC-derived adult mice ('all-iPSC mice'). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This approach allowed us to generate all-iPSC mice from mature B cells, which have until now failed to support the development of exclusively iPSC-derived postnatal animals. Our data show that transcription factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of the resultant iPSCs. More... »

PAGES

398

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.1110

DOI

http://dx.doi.org/10.1038/ng.1110

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003080962

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22387999


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