title: The alteration of H4-K16ac and H3-K27met influences the differentiation of neural stem cells.
abstract: The neural stem cell therapy provides a promising future for patients with central nerve system damage, thus an insight into its differentiation mechanism is urgently needed. Herein, we aimed to identify various histone modifications and reveal their impact on the differentiation of neural stem cells (NSCs) toward neurons. Firstly, we labeled primary NSCs using the stable isotope labeling with amino acids in cell culture (SILAC) technique. Then we induced these NSCs to differentiate by all-trans retinoic acid (atRA) or SB216763. Next, we identified the alteration of histone modifications in early-differentiated NSCs by mass spectrometry and verified them by Western blot. Interestingly, these modification alterations and phenotype changes were found similar in NSCs induced by the two different drugs. More interestingly, during the differentiation process H3-K27met was significantly up-regulated while H4-K16ac was not altered at the global level but down-regulated in some low-abundance combinatorial codes. We inhibited the methyltransferase of H3-K27 and deacetylase of H4-K16 simultaneously and found the differentiation procedure was obviously delayed. The function of H4-K16ac and H3-K27met in NSCs differentiation would be useful to reveal the differentiation mechanism and valuable for further neural stem cell therapy.
authors.affiliation: Department of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109, United States. Electronic address: mingruia@umich.edu.
authors.forename: Mingrui
authors.initials: M
authors.lastname: An
authors.affiliation: Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address: hyshen85@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Shen
authors.affiliation: College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, 310036, China. Electronic address: caojun91@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Toxicology, School of Public Health, Shenyang Medical College, Liaoning, 110034, China. Electronic address: xiaopei2399@163.com.
authors.forename: Xiucong
authors.initials: X
authors.lastname: Pei
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: tcmcyx@126.com.
authors.forename: Yanxu
authors.initials: Y
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China. Electronic address: mashuaipeng1986@126.com.
authors.forename: Shuaipeng
authors.initials: S
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China. Electronic address: baojintao.cbs@163.com.
authors.forename: Jintao
authors.initials: J
authors.lastname: Bao
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China. Electronic address: xuefei.zhang10@gmail.com.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China. Electronic address: baixue_jiayou@163.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China. Electronic address: mayuanhui31@gmail.com.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D006657:Histones / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D006657:Histones; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D014212:Tretinoin
keywords: Differentiation; Histone modifications; NSCs; SILAC