TY - JOUR
T1 - Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors
AU - Johannesson, Bjarki
AU - Sagi, Ido
AU - Gore, Athurva
AU - Paull, Daniel
AU - Yamada, Mitsutoshi
AU - Golan-Lev, Tamar
AU - Li, Zhe
AU - LeDuc, Charles
AU - Shen, Yufeng
AU - Stern, Samantha
AU - Xu, Nanfang
AU - Ma, Hong
AU - Kang, Eunju
AU - Mitalipov, Shoukhrat
AU - Sauer, Mark V.
AU - Zhang, Kun
AU - Benvenisty, Nissim
AU - Egli, Dieter
N1 - Publisher Copyright:
©2014 Elsevier Inc.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84922637049&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2014.10.002
DO - 10.1016/j.stem.2014.10.002
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 25517467
AN - SCOPUS:84922637049
SN - 1934-5909
VL - 15
SP - 634
EP - 642
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 5
ER -