Somatic nucleus reprogramming is significantly improved by m-carboxycinnamic acid bishydroxamide, a histone deacetylase inhibitor.
Somatic cell nuclear transfer (SCNT) has shown tremendous potential for understanding the mechanisms of reprogramming and creating applications in the realms of agriculture, therapeutics, and regenerative medicine, although the efficiency of reprogramming is still low. Somatic nucleus reprogramming is triggered in the short time after transfer into recipient cytoplasm, and therefore, this period is regarded as a key stage for optimizing SCNT. Here we report that CBHA, a histone deacetylase inhibitor, modifies the acetylation status of somatic nuclei and increases the developmental potential of mouse cloned embryos to reach pre- and post-implantation stages. Furthermore, the cloned embryos treated by CBHA displayed higher efficiency in the derivation of nuclear transfer embryonic stem cell lines by promoting outgrowths. More importantly, CBHA increased blastocyst quality compared with trichostatin A, another prevalent histone deacetylase inhibitor reported previously. Use of CBHA should improve the productivity of SCNT for a variety of research and clinical applications, and comparisons of cells with different levels of pluripotency and treated with CBHA versus trichostatin A will facilitate studies of the mechanisms of reprogramming.
Dai
Xiangpeng
X
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Hao
Jie
J
Hou
Xiao-Jun
XJ
Hai
Tang
T
Fan
Yong
Y
Yu
Yang
Y
Jouneau
Alice
A
Wang
Liu
L
Zhou
Qi
Q
D000107:Acetylation; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D054337:Cell Dedifferentiation / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology*; D019976:Cloning, Organism; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053652:Nuclear Transfer Techniques
D002934:Cinnamates; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C111238:carboxycinnamic acid bishydroxamide; C012589:trichostatin A