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Epigenetic memory in induced pluripotent stem cells

Open access
Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., Kim, J., Aryee, M. J., Ji, H., Ehrlich, L. I. R., Yabuuchi, A., Takeuchi, A., Cunniff, K. C., Hongguang, H., Mckinney-Freeman, S., Naveiras, O., Yoon, T. J., Irizarry, R. A., Jung, N., Seita, J., Hanna, J., Murakami, P., Jaenisch, R., Weissleder, R., Orkin, S. H., Weissman, I. L., Feinberg, A. P., Daley, G. Q.·2010·Nature

Abstract

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an ‘epigenetic memory’ of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

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Metadata

Authors
Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., Kim, J., Aryee, M. J., Ji, H., Ehrlich, L. I. R., Yabuuchi, A., Takeuchi, A., Cunniff, K. C., Hongguang, H., Mckinney-Freeman, S., Naveiras, O., Yoon, T. J., Irizarry, R. A., Jung, N., Seita, J., Hanna, J., Murakami, P., Jaenisch, R., Weissleder, R., Orkin, S. H., Weissman, I. L., Feinberg, A. P., & Daley, G. Q.
Venue
Nature
Published
2010-07-19
Volume
467
Issue
7313
Pages
285-290
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2102560467
Cited by
2,313
References
5
FWCI
98.89
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Epigenetic memory in induced pluripotent stem cells. https://app.cochat.ai/papers/10.1038/nature09342
The paper
Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., Kim, J., Aryee, M. J., Ji, H., Ehrlich, L. I. R., Yabuuchi, A., Takeuchi, A., Cunniff, K. C., Hongguang, H., Mckinney-Freeman, S., Naveiras, O., Yoon, T. J., Irizarry, R. A., Jung, N., . . . Daley, G. Q. (2010). Epigenetic memory in induced pluripotent stem cells. Nature. https://doi.org/10.1038/nature09342

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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