Dataset Information

Cellular and Molecular Probing of Intact Human Organs.

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.

SUBMITTER: Zhao S

PROVIDER: S-EPMC7557154 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Cellular and Molecular Probing of Intact Human Organs.

Zhao Shan S Todorov Mihail Ivilinov MI Cai Ruiyao R -Maskari Rami Ai RA Steinke Hanno H Kemter Elisabeth E Mai Hongcheng H Rong Zhouyi Z Warmer Martin M Stanic Karen K Schoppe Oliver O Paetzold Johannes Christian JC Gesierich Benno B Wong Milagros N MN Huber Tobias B TB Duering Marco M Bruns Oliver Thomas OT Menze Bjoern B Lipfert Jan J Puelles Victor G VG Wolf Eckhard E Bechmann Ingo I Ertürk Ali A

Cell 20200213 4

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 ...[more]

PMID: 32059778

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Project description:Human African Trypanosomiasis (HAT) is a disease caused by the extracellular parasite Trypanosoma brucei that affects the central nervous system (CNS) during the chronic stage of the infection, inducing neuroinflammation, coma, and death if left untreated. However, little is known about the structural change happening in the brain as result of the infection. So far, infection-induced neuroinflammation has been observed with conventional methods, such as immunohistochemistry, electron microscopy, and 2-photon microscopy only in small portions of the brain, which may not be representative of the disease. In this paper, we have used a newly-developed light-sheet illuminator to image the level of neuroinflammation in chronically infected mice and compared it to naïve controls. This system was developed for imaging in combination with the Mesolens objective lens, providing fast sub-cellular resolution for tens of mm3-large imaging volumes. The mouse brain specimens were cleared using CUBIC+, followed by antibody staining to locate Glial Fibrillary Acid Protein (GFAP) expressing cells, primarily astrocytes and ependymocytes, used here as a proxy for cell reactivity and gliosis. The large capture volume allowed us to detect GFAP+ cells and spatially resolve the response to T. brucei infection. Based on morphometric analyses and spatial distribution of GFAP+ cells, our data demonstrates a significant increase in cell dendrite branching around the lateral ventricle, as well as dorsal and ventral third ventricles, that are negatively correlated with the branch extension in distal sites from the circumventricular spaces. To our knowledge, this is the first report highlighting the potential of light-sheet mesoscopy to characterise the inflammatory responses of the mouse brain to parasitic infection at the cellular level in intact cleared organs, opening new avenues for the development of new mesoscale imaging techniques for the study of host-pathogen interactions.

Dataset Information

Cellular and Molecular Probing of Intact Human Organs.

Publications

Cellular and Molecular Probing of Intact Human Organs.

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