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Cell Stem Cell. 2014 Nov 6;15(5):634-42. doi: 10.1016/j.stem.2014.10.002. Epub 2014 Nov 6.

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

Author information

1
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
2
Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
3
Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA.
4
Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
5
Departments of Systems Biology and Biomedical Informatics, JP Sulzberger Columbia Genome Center, Columbia University Medical Center, New York, NY 10032, USA.
6
Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
7
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
8
Center for Women's Reproductive Care, College of Physicians and Surgeons, Columbia University, New York, NY 10019, USA.
9
Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. Electronic address: nissimb@cc.huji.ac.il.
10
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: d.egli@nyscf.org.

Abstract

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.

PMID:
25517467
DOI:
10.1016/j.stem.2014.10.002
[Indexed for MEDLINE]
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