Cellular and Molecular ProbingofIntact Human Organs

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