Dissecting cross-lineage tumourigenesis under p53 inactivation through single-cell multi-omics and spatial transcriptomics.

Journal: Clinical and translational medicine
Published Date:

Abstract

BACKGROUND: Tumour suppressor genes, exemplified by TP53 (encoding the human p53), function as critical guardians against tumourigenesis. Germline TP53-inactivating mutations underlie Li-Fraumeni syndrome, a hereditary cancer predisposition disorder characterised by early-onset pan-tissue malignancies. However, the context-dependent tumour-suppressive mechanisms of p53 remain incompletely elucidated. This study aims to investigate the disruption of cellular homeostasis and tumourigenic mechanisms following p53 inactivation across distinct cell lineages.

Authors

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Guodong Zhang
  • Jiaqi Li
    Department of Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of 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.
  • Xing Fang
    Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • Lifeng Ma
  • Yuan Liao
    College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Bioelectrochemistry and Environmental Analysis of Gansu Province, Lanzhou 730070, 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.
  • Haofu Niu
    Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • E Weigao
    Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 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.
  • Lei Yang
    George Mason University.
  • Shuang Zhang
    The Department of Ophthalmology of the First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, China.
  • Tingyue Zhang
    Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • Yincong Zhou
    Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
  • Qi Zhang
    Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • He Huang
  • Hongwei Ouyang
    Department of Sports Medicine of the First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China. hwoy@zju.edu.cn.
  • Ming Chen
    Department of Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
  • Tingbo Liang
    Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, State Key Laboratory of Modern Optical Instrumentation, Zhejiang University School of Medicine, Hangzhou 310003, China.
  • Jinrong Peng
    MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, 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.
  • 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.
  • 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.