Profiling post-translational modifications of histones in neural differentiation of embryonic stem cells using liquid chromatography-mass spectrometry

Shuzhen Zheng; Ming Sun; Kai Zhang; Junjie Gu; Zhenchang Guo; Shanshan Tian; Guijin Zhai; Xiwen He; Ying Jin; Yukui Zhang

doi:10.1016/j.jchromb.2016.02.022

Profiling post-translational modifications of histones in neural differentiation of embryonic stem cells using liquid chromatography-mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 1:1017-1018:36-44. doi: 10.1016/j.jchromb.2016.02.022. Epub 2016 Feb 18.

Authors

Shuzhen Zheng¹, Ming Sun², Kai Zhang³, Junjie Gu², Zhenchang Guo⁴, Shanshan Tian⁴, Guijin Zhai⁴, Xiwen He¹, Ying Jin², Yukui Zhang⁵

Affiliations

¹ Department of Chemistry, Nankai University, Tianjin 300071, China.
² Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
³ Department of Chemistry, Nankai University, Tianjin 300071, China; 2011Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, 300070 Tianjin, China. Electronic address: kzhang@tmu.edu.cn.
⁴ 2011Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, 300070 Tianjin, China.
⁵ Department of Chemistry, Nankai University, Tianjin 300071, China; National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, China.

PMID: 26945132
DOI: 10.1016/j.jchromb.2016.02.022

Abstract

The neural differentiation of embryonic stem cells (ESCs) is of great significance for understanding of the mechanism of diseases. Histone post-translational modifications (HPTMs) play a key role in the regulation of ESCs differentiation. Here, we combined the stable isotope chemical derivatization with nano-HPLC-mass spectrometry (MS) for comprehensive analysis and quantification of histone post-translational modifications (HPTMs) in mouse embryonic stem cells (mESCs) and neural progenitor cells (mNPCs) that was derived from ESCs. We identified 85 core HPTM sites in ESCs and 78HPTM sites in NPCs including some novel lysine modifications. Our quantitative analysis results further revealed the changes of HPTMs from ESCs to NPCs and suggested effect of combinational HPTMs in the differentiation. This study demonstrates that HPLC-MS-based quantitative proteomics has a considerable advantage on quantification of combinational PTMs and expands our understanding of HPTMs in the differentiation.

Keywords: Cell differentiation; Derivatization; HPLC–MS/MS; Proteomics; Quantitative analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Cell Differentiation*
Chromatography, High Pressure Liquid / methods*
Embryonic Stem Cells / cytology*
Histones / metabolism*
Mice
Molecular Sequence Data
Protein Processing, Post-Translational*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tandem Mass Spectrometry / methods*

Substances

Histones