Recommended Conferences

Human Genetics and Genetic Disorders

Miami, USA

Tissue Engineering and Regenerative Medicine

Chicago, USA
Related Subjects
 

Epigenetic memory in induced pluripotent stem cells

Author(s): Kim K, Doi A, Wen B, Ng K, Zhao R, et al.

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.

Similar Articles

Naive and primed pluripotent states

Author(s): Nichols J, Smith A

MicroRNAs: key regulators of stem cells

Author(s): Gangaraju VK, Lin H

Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse

Author(s): Stadtfeld M, Maherali N, Breault DT, Hochedlinger K

Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells

Author(s): Chan EM, Ratanasirintrawoot S, Park IH, Manos PD, Loh YH, et al.

Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution

Author(s): Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, et al.

Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells

Author(s): Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, et al.

Immunogenicity of induced pluripotent stem cells

Author(s): Zhao T, Zhang ZN, Rong Z, Xu Y

Nuclear transfer to eggs and oocytes

Author(s): Gurdon JB, Wilmut I

CAF-1 is essential for heterochromatin organization in pluripotent embryonic cells

Author(s): Houlard M, Berlivet S, Probst AV, Quivy JP, Héry P, et al.

Acetylation-dependent chromatin reorganization by BRDT, a testis-specific bromodomain-containing protein

Author(s): Pivot-Pajot C, Caron C, Govin J, Vion A, Rousseaux S, et al.

Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors

Author(s): Jude CD, Climer L, Xu D, Artinger E, Fisher JK, et al.

Histone H4-K16 acetylation controls chromatin structure and protein interactions

Author(s): Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, et al.

Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs

Author(s): Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, et al.

Patient-specific induced pluripotent stem-cell models for long-QT syndrome

Author(s): Moretti A, Bellin M, Welling A, Jung CB, Lam JT, et al.

Modelling the long QT syndrome with induced pluripotent stem cells

Author(s): Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, et al.