Journal
CELL STEM CELL
Volume 23, Issue 3, Pages 343-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2018.06.008
Keywords
-
Categories
Funding
- NIH [R01HD092465]
- HHMI
- JSPS KAKENHI [JP16H06146]
- Zhejiang Provincial Natural Science Foundation of China [LR18C060001]
- Charles A. King Trust postdoctoral research fellowship
Ask authors/readers for more resources
Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), although the live birth rate is relatively low. Recent studies have identified H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT. Here we overcome these barriers using a combination of Xist knockout donor cells and overexpression of Kdm4 to achieve more than 20% efficiency of mouse SCNT. However, post-implantation defects and abnormal placentas were still observed, indicating that additional epigenetic barriers impede SCNT cloning. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified abnormally methylated regions in SCNT embryos despite successful global reprogramming of the methylome. Strikingly, allelic transcriptomic and ChIP-seq analyses of pre-implantation SCNT embryos revealed complete loss of H3K27me3 imprinting, which may account for the postnatal developmental defects observed in SCNT embryos. Together, these results provide an efficient method for mouse cloning while paving the way for further improving SCNT efficiency.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available