Construction of a cross-species cell landscape at single-cell level

Author:

Wang Renying1,Zhang Peijing12,Wang Jingjing12,Ma Lifeng1,E Weigao1,Suo Shengbao3,Jiang Mengmeng12,Li Jiaqi1,Chen Haide12,Sun Huiyu1,Fei Lijiang1,Zhou Ziming1,Zhou Yincong4,Chen Yao5,Zhang Weiqi6,Wang Xinru1,Mei Yuqing1,Sun Zhongyi1,Yu Chengxuan1,Shao Jikai1,Fu Yuting1,Xiao Yanyu1,Ye Fang1,Fang Xing1ORCID,Wu Hanyu1,Guo Qile7,Fang Xiunan1,Li Xia1,Gao Xianzhi8,Wang Dan9,Xu Peng-Fei9ORCID,Zeng Rui10,Xu Gang10,Zhu Lijun11,Wang Lie8,Qu Jing12,Zhang Dan5ORCID,Ouyang Hongwei713,Huang He1,Chen Ming4,NG Shyh-Chang12,Liu Guang-Hui12ORCID,Yuan Guo-Cheng14ORCID,Guo Guoji12713ORCID,Han Xiaoping113

Affiliation:

1. Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China

2. Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, 311121, China

3. Guangzhou Laboratory , Guangzhou 510005, China

4. College of Life Sciences, Zhejiang University , Hangzhou 310058, China

5. Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310006, PR China

6. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation , Beijing 100101, China

7. Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University , Hangzhou 314400, China

8. Institute of Immunology and Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou 310058, China

9. Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine , Hangzhou 310058, China

10. Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030, China

11. Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou 310058, China

12. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China

13. Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine , Hangzhou, Zhejiang 310058, China

14. Department of Genetics and Genomic Sciences, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai , NY, NY 10029, USA

Abstract

Abstract Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal—Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.

Funder

National Natural Science Foundation of China

National Key Research and Development Program

Publisher

Oxford University Press (OUP)

Subject

Genetics

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