Single-Cell Transcriptome Analysis Reveals Six Subpopulations Reflecting Distinct Cellular Fates in Senescent Mouse Embryonic Fibroblasts.
Wei Chen, Xuefei Wang, Gang Wei, Yin Huang, Yufang Shi, Dan Li, Shengnu Qiu, Bin Zhou, Junhong Cao, Meng Chen, Pengfei Qin, Wenfei Jin, Ting Ni
Author Information
Wei Chen: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Xuefei Wang: Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Gang Wei: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Yin Huang: Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Yufang Shi: Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Dan Li: Field Application Department, Fluidigm (Shanghai) Instrument Technology Co., Ltd., Shanghai, China.
Shengnu Qiu: Division of Biosciences, Faculty of Life Sciences, University College London, London, United Kingdom.
Bin Zhou: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Junhong Cao: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Meng Chen: Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Pengfei Qin: Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Wenfei Jin: Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Ting Ni: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Replicative senescence is a hallmark of aging, which also contributes to individual aging. Mouse embryonic fibroblasts (MEFs) provide a convenient replicative senescence model. However, the heterogeneity of single MEFs during cellular senescence has remained unclear. Here, we conducted single-cell RNA sequencing on senescent MEFs. Principal component analysis showed obvious heterogeneity among these MEFs such that they could be divided into six subpopulations. Three types of gene expression analysis revealed distinct expression features of these six subpopulations. Trajectory analysis revealed three distinct lineages during MEF senescence. In the main lineage, some senescence-associated secretory phenotypes were upregulated in a subset of cells from senescent clusters, which could not be distinguished in a previous bulk study. In the other two lineages, a possibility of escape from cell cycle arrest and coupling between translation-related genes and ATP synthesis-related genes were also discovered. Additionally, we found co-expression of transcription factor HOXD8 coding gene and its potential target genes in the main lineage. Overexpression of led to senescence-associated phenotypes, suggesting HOXD8 is a new regulator of MEF senescence. Together, our single-cell sequencing on senescent MEFs largely expanded the knowledge of a basic cell model for aging research.
