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

Bjarki Johannesson; Ido Sagi; Athurva Gore; Daniel Paull; Mitsutoshi Yamada; Tamar Golan-Lev; Zhe Li; Charles LeDuc; Yufeng Shen; Samantha Stern; Nanfang Xu; Hong Ma; Eunju Kang; Shoukhrat Mitalipov; Mark V Sauer; Kun Zhang; Nissim Benvenisty; Dieter Egli

doi:10.1016/j.stem.2014.10.002

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

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

Authors

Bjarki Johannesson¹, Ido Sagi², Athurva Gore³, Daniel Paull¹, Mitsutoshi Yamada¹, Tamar Golan-Lev², Zhe Li³, Charles LeDuc⁴, Yufeng Shen⁵, Samantha Stern¹, Nanfang Xu⁶, Hong Ma⁷, Eunju Kang⁷, Shoukhrat Mitalipov⁷, Mark V Sauer⁸, Kun Zhang³, Nissim Benvenisty⁹, Dieter Egli¹⁰

Affiliations

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: [email protected].
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: [email protected].

PMID: 25517467
DOI: 10.1016/j.stem.2014.10.002

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Base Sequence
Clone Cells
DNA Methylation / genetics
Gene Expression Regulation
Genetic Loci
Genomic Imprinting / genetics*
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism
Male
Molecular Sequence Data
Mutation Rate*
Nuclear Transfer Techniques*
Open Reading Frames / genetics*
Pluripotent Stem Cells / cytology*
Pluripotent Stem Cells / metabolism

Associated data

GDB/GSE61657
GEO/GSE28024
GEO/GSE42077