Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors.

Authors:
Bjarki Johannesson
Bjarki Johannesson
University of Heidelberg
Germany
Ido Sagi
Ido Sagi
Silberman Institute of Life Sciences
Israel
Athurva Gore
Athurva Gore
University of California at San Diego
Irvine | United States
Daniel Paull
Daniel Paull
Johns Hopkins University
United States
Mitsutoshi Yamada
Mitsutoshi Yamada
Keio University School of Medicine
Japan
Tamar Golan-Lev
Tamar Golan-Lev
The International Stem Cell Research Institute
United States
Zhe Li
Zhe Li
University of California
United States
Charles LeDuc
Charles LeDuc
Columbia University
United States

Cell Stem Cell 2014 Nov 6;15(5):634-42. Epub 2014 Nov 6.

The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA; Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address:

The recent finding that reprogrammed human pluripotent stem cells can be derived by nuclear transfer into human oocytes as well as by induced expression of defined factors has revitalized the debate on whether one approach might be advantageous over the other. Here we compare the genetic and epigenetic integrity of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal, and adult origin. The two cell types showed similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs had comparable numbers of de novo coding mutations, but significantly more than parthenogenetic ESCs. As iPSCs, NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of derivation approach.

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http://dx.doi.org/10.1016/j.stem.2014.10.002DOI Listing
November 2014
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