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.