Combined Proteomic and Phosphoproteomic Characterization of the Molecular Regulators and Functional Modules During Pancreatic Progenitor Cell Development

He，Qian1,2,3,5; Xu，Shaohang6; He，Fei1,3,5; Wu，Zubiao1,3,5; Wu，Fujian1,3,4,5; Zhou，Ruo6; Zhou，Baojin7; Li，Furong1,3,5; Yang，Xiaofei1,3,5

2024-01-05

10.1021/acs.jproteome.3c00309

Journal of Proteome Research   影响因子和分区

1535-3893

1535-3907

Differentiated multipotent pancreatic progenitors have major advantages for both modeling pancreas development and preventing or treating diabetes. Despite significant advancements in inducing the differentiation of human pluripotent stem cells into insulin-producing cells, the complete mechanism governing proliferation and differentiation remains poorly understood. This study used large-scale mass spectrometry to characterize molecular processes at various stages of human embryonic stem cell (hESC) differentiation toward pancreatic progenitors. hESCs were induced into pancreatic progenitor cells in a five-stage differentiation protocol. A high-performance liquid chromatography-mass spectrometry platform was used to undertake comprehensive proteome and phosphoproteome profiling of cells at different stages. A series of bioinformatic explorations, including coregulated modules, gene regulatory networks, and phosphosite enrichment analysis, were then conducted. A total of 27,077 unique phosphorylated sites and 8122 proteins were detected, including several cyclin-dependent kinases at the initial stage of cell differentiation. Furthermore, we discovered that ERK1, a member of the MAPK cascade, contributed to proliferation at an early stage. Finally, Western blotting confirmed that the phosphosites from SIRT1 and CHEK1 could inhibit the corresponding substrate abundance in the late stage. Thus, this study extends our understanding of the molecular mechanism during pancreatic cell development.

high-performance liquid chromatography−mass spectrometry pancreatic progenitor cell phosphoproteomics proteomics

SCI

英语

第一

BIOLOGY & BIOCHEMISTRY

2-s2.0-85179822907

Scopus

1.Translational Medicine Collaborative Innovation Center,Shenzhen People’s Hospital (The First Affiliated Hospital,Southern University of Science and Technology,The Second Clinical Medical College of Jinan University),Shenzhen,518055,China
2.School of Food and Drug,Shenzhen Polytechnic,Shenzhen,518055,China
3.Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy,Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation,Shenzhen Immune Cell Therapy Public Service Platform,Shenzhen,518020,China
4.Post-doctoral Scientific Research Station of Basic Medicine,Jinan University,Guangzhou,510632,China
5.Institute of Health Medicine,Southern University of Science and Technology,Shenzhen,518055,China
6.Deepxomics Co.,Ltd.,Shenzhen,518000,China
7.Experiment Center for Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China

He，Qian,Xu，Shaohang,He，Fei,et al. Combined Proteomic and Phosphoproteomic Characterization of the Molecular Regulators and Functional Modules During Pancreatic Progenitor Cell Development[J]. Journal of Proteome Research,2024,23(1):40-51.

He，Qian.,Xu，Shaohang.,He，Fei.,Wu，Zubiao.,Wu，Fujian.,...&Yang，Xiaofei.(2024).Combined Proteomic and Phosphoproteomic Characterization of the Molecular Regulators and Functional Modules During Pancreatic Progenitor Cell Development.Journal of Proteome Research,23(1),40-51.

He，Qian,et al."Combined Proteomic and Phosphoproteomic Characterization of the Molecular Regulators and Functional Modules During Pancreatic Progenitor Cell Development".Journal of Proteome Research 23.1(2024):40-51.