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

Stadtfeld, M., Apostolou, E., Ferrari, F., Choi, J., Walsh, R. M., Chen, T., Oi, S., Kim, S. Y., Bestor, T., Shioda, T., Park, P. J., Hochedlinger, K. (March 2012) Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells. Nature Genetics, 44. pp. 398-405. ISSN 10614036 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22387999
DOI: 10.1038/ng.1110

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.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells

organism description > animal
organs, tissues, organelles, cell types and functions > cell types and functions
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: Matt Covey
Date: 4 March 2012
Date Deposited: 18 Jan 2013 16:50
Last Modified: 18 Jan 2013 16:50
PMCID: PMC3538378
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27052

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