The human body is estimated to have more than 1 trillion cells with different properties. The non-uniform characteristics observed among cells are referred to as cellular heterogeneity. Understanding cellular heterogeneity, especially linked to 3D anatomical information, provides us with increased understanding of how life produces highly organized tissues with complex functions. In a clinical context, it can help us understand the heterogeneity of cancer cells, i.e. tumor heterogeneity, to make new treatment strategies for cancer.
Recent developments in biotechnology and computer science have gradually unlocked the limits and have allowed us to visualize cells and complex gene expressions in whole animals and human tissues. For example, recent tissue clearing techniques (CLARITY, CUBIC, iDISCO etc., see references) allow us to get optical sections of whole bodies without cutting tissue, and analyze image data in a 3D manner. New fast image acquisition methods using light-sheet microscopy allow us to image whole tissue at more than 100 times faster than conventional microscopy. However, applying these technologies to researches is still challenging and time-consuming due to difficulties in sample handling.
In this project, we aim to develop a new 3D imaging pipeline that is easily accessible from both basic and clinical research to analyze cellular heterogeneity in whole tissues and clinical samples.
Applications for this project are invited from master students. The students will be trained to learn whole tissue imaging techniques including tissue clearing techniques, light-sheet microscopy and 3D image processing and analysis.

References

CLARITY
Structural and molecular interrogation of intact biological systems.
Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ, Mirzabekov JJ, Zalocusky KA, Mattis J, Denisin AK, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, Deisseroth K.
Nature. 2013 May 16;497(7449):332-7. doi: 10.1038/nature12107. Epub 2013 Apr 10.
PMID: 23575631

CUBIC
Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis.
Susaki EA, Tainaka K, Perrin D, Kishino F, Tawara T, Watanabe TM, Yokoyama C, Onoe H, Eguchi M, Yamaguchi S, Abe T, Kiyonari H, Shimizu Y, Miyawaki A, Yokota H, Ueda HR.
Cell. 2014 Apr 24;157(3):726-39. doi: 10.1016/j.cell.2014.03.042. Epub 2014 Apr 17.
PMID: 24746791

iDisco
iDISCO: a simple, rapid method to immunolabel large tissue samples for volume imaging.
Renier N, Wu Z, Simon DJ, Yang J, Ariel P, Tessier-Lavigne M.
Cell. 2014 Nov 6;159(4):896-910. doi: 10.1016/j.cell.2014.10.010. Epub 2014 Oct 30.
PMID: 25417164

Custom-built light sheet microscope (COLM)
Advanced CLARITY for rapid and high-resolution imaging of intact tissues.
Tomer R, Ye L, Hsueh B, Deisseroth K.
Nat Protoc. 2014 Jul;9(7):1682-97. doi: 10.1038/nprot.2014.123. Epub 2014 Jun 19.
PMID: 24945384