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

First Author  Wang Y Year  2021
Journal  Cell Volume  184
Issue  26 Pages  6361-6377.e24
PubMed ID  34875226 Mgi Jnum  J:328679
Mgi Id  MGI:6844854 Doi  10.1016/j.cell.2021.11.024
Citation  Wang Y, et al. (2021) EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization. Cell 184(26):6361-6377.e24
abstractText  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 mum) 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.
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