Deep learning of cross-species single-cell landscapes identifies conserved regulatory programs underlying cell types.

Journal: Nature genetics
PMID: 36229673

Abstract

Despite extensive efforts to generate and analyze reference genomes, genetic models to predict gene regulation and cell fate decisions are lacking for most species. Here, we generated whole-body single-cell transcriptomic landscapes of zebrafish, Drosophila and earthworm. We then integrated cell landscapes from eight representative metazoan species to study gene regulation across evolution. Using these uniformly constructed cross-species landscapes, we developed a deep-learning-based strategy, Nvwa, to predict gene expression and identify regulatory sequences at the single-cell level. We systematically compared cell-type-specific transcription factors to reveal conserved genetic regulation in vertebrates and invertebrates. Our work provides a valuable resource and offers a new strategy for studying regulatory grammar in diverse biological systems.

Authors

  • Jiaqi Li
    Department of Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.
  • Jingjing Wang
    Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China.
  • Peijing Zhang
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Renying Wang
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Yuqing Mei
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Zhongyi Sun
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Lijiang Fei
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Mengmeng Jiang
    Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital of Fudan University, Fudan University, No 130, Dongan Rd, Xuhui District, Shanghai, 200032, P.R. of China.
  • Lifeng Ma
  • Weigao E
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Haide Chen
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xinru Wang
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Yuting Fu
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Hanyu Wu
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Daiyuan Liu
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xueyi Wang
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Jingyu Li
    Medical Technology Department, Qiqihar Medical University, Qiqihar 161006, Heilongjiang, China.
  • Qile Guo
    Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
  • Yuan Liao
    College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Bioelectrochemistry and Environmental Analysis of Gansu Province, Lanzhou 730070, China.
  • Chengxuan Yu
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Danmei Jia
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Jian Wu
    Department of Medical Technology, Jiangxi Medical College, Shangrao, Jiangxi, China.
  • Shibo He
    College of Control Science and Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, China. s18he@zju.edu.cn.
  • Huanju Liu
    Women's Hospital and Institute of Genetics, Zhenjiang University School of Medicine, Hangzhou, China.
  • Jun Ma
    State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.
  • Kai Lei
    School of Electronics and Computer Engineering, Peking University Shenzhen Graduate School, Shenzhen, China. Electronic address: leik@pkusz.edu.cn.
  • Jiming Chen
    College of Control Science and Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, China.
  • Xiaoping Han
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. xhan@zju.edu.cn.
  • Guoji Guo
    Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. ggj@zju.edu.cn.

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