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Wang Y, Eddison M, Fleishman G, et al. EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization. Cell. 2021;doi: 10.1016/j.cell.2021.11.024.
Wang, Y., Eddison, M., Fleishman, G., Weigert, M., Xu, S., Wang, T., Rokicki, K., Goina, C., Henry, F. E., Lemire, A. L., Schmidt, U., Yang, H., Svoboda, K., Myers, E. W., Saalfeld, S., Korff, W., Sternson, S. M., & Tillberg, P. W. (2021). EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization. Cell, . https://doi.org/10.1016/j.cell.2021.11.024
Wang, Yuhan, et al. "EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization." Cell vol. (2021). doi: https://doi.org/10.1016/j.cell.2021.11.024
Wang Y, Eddison M, Fleishman G, Weigert M, Xu S, Wang T, Rokicki K, Goina C, Henry FE, Lemire AL, Schmidt U, Yang H, Svoboda K, Myers EW, Saalfeld S, Korff W, Sternson SM, Tillberg PW. EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization. Cell. 2021 Dec 01; doi: 10.1016/j.cell.2021.11.024. Epub 2021 Dec 01. PMID: 34875226.
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Cell. 2021 Dec 01; doi: 10.1016/j.cell.2021.11.024. Epub 2021 Dec 01.

EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization.

Cell

Yuhan Wang, Mark Eddison, Greg Fleishman, Martin Weigert, Shengjin Xu, Tim Wang, Konrad Rokicki, Cristian Goina, Fredrick E Henry, Andrew L Lemire, Uwe Schmidt, Hui Yang, Karel Svoboda, Eugene W Myers, Stephan Saalfeld, Wyatt Korff, Scott M Sternson, Paul W Tillberg

Affiliations

  1. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
  2. Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Institute of Bioengineering, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland.
  3. Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
  4. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
  5. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
  6. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: [email protected].

PMID: 34875226 DOI: 10.1016/j.cell.2021.11.024

Abstract

Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developed Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 μm) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine spatially and molecularly defined subregions. EASI-FISH also facilitates iterative reanalysis of scRNA-seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: 3D segmentation; Fluorescence in situ hybridization; RNA; brain; brain anatomy; cell type; expansion microscopy; lateral hypothalamus; transcriptomics

Conflict of interest statement

Declaration of interests P.W.T. is an inventor on patents related to this study (10,309,879; 10,317,321; 10,563,257; 10,059,990).

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