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. |