| Title | SIRT6 deficiency results in developmental retardation cynomolgus monkeys |
| Authors | Zhang, Weiqi Wan, Haifeng Feng, Guihai Qu, Jing Wang, Jiaqiang Jing, Yaobin Ren, Ruotong Liu, Zunpeng Zhang, Linlin Chen, Zhiguo Wang, Shuyan Zhao, Yong Wang, Zhaoxia Yuan, Yun Zhou, Qi Li, Wei Liu, Guang-Hui Hu, Baoyang |
| Affiliation | Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing, Peoples R China. Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China. Univ Chinese Acad Sci, Beijing, Peoples R China. Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China. Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp,Cell Therapy Ctr, Beijing, Peoples R China. Sun Yat Sen Univ, Sch Life Sci, Dept Biochem, Key Lab Gene Engn,Minist Educ, Guangzhou, Guangdong, Peoples R China. Peking Univ, Dept Neurol, Hosp 1, Beijing, Peoples R China. Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing, Peoples R China. Li, W Hu, BY (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China. Li, W Liu, GH Hu, BY (reprint author), Univ Chinese Acad Sci, Beijing, Peoples R China. Li, W Liu, GH Hu, BY (reprint author), Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China. Liu, GH (reprint author), Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp,Cell Therapy Ctr, Beijing, Peoples R China. |
| Keywords | ONE-STEP GENERATION LARGE GENE LISTS RHESUS-MONKEYS RNA CELLS SIRTUINS MICE CTCF HEALTHSPAN EXPRESSION |
| Issue Date | 2018 |
| Publisher | NATURE |
| Citation | NATURE. 2018, 560(7720), 661-+. |
| Abstract | SIRT6 acts as a longevity protein in rodents(1,2). However, its biological function in primates remains largely unknown. Here we generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model using a CRISPR-Cas9-based approach. SIRT6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19 (a developmental repressor), and we were able to recapitulate this process in a human neural progenitor cell differentiation system. SIRT6 deficiency results in histone hyperacetylation at the imprinting control region of H19, CTCF recruitment and upregulation of H19. Our results suggest that SIRT6 is involved in regulating development in nonhuman primates, and may provide mechanistic insight into human perinatal lethality syndrome. |
| URI | http://hdl.handle.net/20.500.11897/517694 |
| ISSN | 0028-0836 |
| DOI | 10.1038/s41586-018-0437-z |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第一医院 |
