Induced pluripotent stem-induced cells show better constitutive heterochromatin remodeling and developmental potential after nuclear transfer than their parental cells.
Recently, reprogramming of somatic cells from a differentiated to pluripotent state by overexpression of specific external transcription factors has been accomplished. It has been widely speculated that an undifferentiated state may make donor cells more efficient for nuclear transfer. To test this hypothesis, we derived induced pluripotent stem cells (iPS cells) from several somatic cell lines: mouse embryonic fibroblast (MEF), adult tail tip fibroblast (TTF), and brain neural stem cells (NSCs). Three dimensional (3D)-fluorescent in situ hybridization (FISH) and quantitative-FISH (Q-FISH) were then used to evaluate constitutive (pericentric and telomeric) heterochromatin organization in these iPS cells and in their parental differentiated cells. Here, we show that important nuclear remodeling and telomeres rejuvenation occur in these iPS cells regardless of their parental origin. When we used these cells as donors for nuclear transfer, we produced live-born cloned mice at much higher rates with the iPS-induced cells than with the parental cell lines. Interestingly, we noticed that developmental potential after nuclear transfer could be correlated with telomere length of the donor cells. Altogether, our findings suggest that constitutive heterochromatin organization from differentiated somatic cells can be reprogrammed to the pluripotent state by induction of iPS cells, which in turn support nuclear transfer procedure quite efficiently.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zichuan
Z
Liu
Haifeng
H
Wan
Eryao
E
Wang
Xiaoyang
X
Zhao
Chenhui
C
Ding
Shuya
S
Zhou
Tianda
T
Li
Ling
L
Shuai
Chunjing
C
Feng
Yang
Y
Yu
Qi
Q
Zhou
Nathalie
N
Beaujean
D000818:Animals; D000831:Animals, Newborn; D001755:Blastocyst / Q000378:metabolism; D001835:Body Weight; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002999:Clone Cells; D005260:Female; D006570:Heterochromatin / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053652:Nuclear Transfer Techniques; D035845:Research Embryo Creation; D059505:Telomere Homeostasis
D006570:Heterochromatin