Epigenetic memory in induced pluripotent stem cells

By K. Kim, A. Doi, Bo Wen, K. Ng, Rui Zhao, Patrick Cahan, Jaeseob Kim, Martin J. Aryee, Hong Ji, L. R. Ehrlich and 18 more. Nature, 2010

2,357 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0623a5f8496f2da677b372c7d490723818cb7104

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Citations in the corpus

Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming (2012, neutral): “…maturation include the use of small molecules such as triiodothyronine binding thyroid hormone receptors (Lee et al., 2010), overexpression or downregulation of specific genes (Yamanaka et al., 2008), and extrinsic cues from other noncardiac cells, including endothelial cells (Kim et al., 2010a).”
Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging (2013, positive): “…such as methylation levels at particular CpG sites that have been reported to predict donor age across multiple tissues (Hannum et al., 2013; Koch and Wagner, 2011) or methylation patterns reported to reflect epigenetic memory in iPSCs of donor cell fate (Kim et al., 2010; Polo et al., 2010).”
Induced pluripotency: history, mechanisms, and applications. (2010, background): “Notably, continuous passaging of iPSCs (Polo et al. 2010) or the treatment of cells with chromatin-modifying drugs (Kim et al. 2010) attenuated these differences.”
Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, positive): “…epigenetic memory, these technical attributes of incomplete reprogramming can be erased following additional Cell 143, November 12, 2010 ª2010 Elsevier Inc. 519 cell division or by supplementing other exogenous factors during reprogramming (Silva et al., 2009; Polo et al., 2010; Kim et al., 2010).”
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