Cellular and Molecular Probing of Intact Human Organs.

Journal: Cell
Published Date: Feb 20, 2020

Abstract

Optical tissue transparency permits scalable cellular and molecular investigation of complex tissues in 3D. Adult human organs are particularly challenging to render transparent because of the accumulation of dense and sturdy molecules in decades-aged tissues. To overcome these challenges, we developed SHANEL, a method based on a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to render the intact adult human brain and kidney transparent and perform 3D histology with antibodies and dyes in centimeters-depth. Thereby, we revealed structural details of the intact human eye, human thyroid, human kidney, and transgenic pig pancreas at the cellular resolution. Furthermore, we developed a deep learning pipeline to analyze millions of cells in cleared human brain tissues within hours with standard lab computers. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of large intact mammalian organs.

Authors

  • Shan Zhao
    Department of Mathematics, University of Alabama, Tuscaloosa, AL 35487-0350, USA.
  • Mihail Ivilinov Todorov
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Graduate School of Systemic Neurosciences (GSN), 82152 Munich, Germany.
  • Ruiyao Cai
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Rami Ai -Maskari
    Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Department of Computer Science, Technical University of Munich (TUM), 81675 Munich, Germany; Center for Translational Cancer Research (TranslaTUM) of the TUM, 80798 Munich, Germany; Graduate School of Bioengineering, Technical University of Munich (TUM), 85748 Munich, Germany.
  • Hanno Steinke
    Institute of Anatomy, University of Leipzig, 04109 Leipzig, Germany.
  • Elisabeth Kemter
    Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), 85764 Oberschleißheim, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
  • Hongcheng Mai
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Zhouyi Rong
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Martin Warmer
    Helmholtz Pioneer Campus, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Karen Stanic
    Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Oliver Schoppe
    Department of Informatics, Technical University of Munich, 85748 Munich, Germany; Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
  • Johannes Christian Paetzold
    Department of Computer Science, Technical University of Munich (TUM), Munich, Germany.
  • Benno Gesierich
    Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Milagros N Wong
    III. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Tobias B Huber
    III. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Marco Duering
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
  • Oliver Thomas Bruns
    Helmholtz Pioneer Campus, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Bjoern Menze
  • Jan Lipfert
    Department of Physics and Center for Nanoscience, Ludwig Maximilian University of Munich (LMU), 80799 Munich, Germany.
  • Victor G Puelles
    III. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department of Nephrology, Monash Health, and Center for Inflammatory Diseases, Monash University, Melbourne VIC 3168, Australia.
  • Eckhard Wolf
    Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), 85764 Oberschleißheim, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
  • Ingo Bechmann
    Institute of Anatomy, University of Leipzig, 04109 Leipzig, Germany.
  • Ali Ertürk
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address: erturk@helmholtz-muenchen.de.

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