A 3-dimensional molecular cartography of human cerebral organoids revealed by double-barcoded spatial transcriptomics

Abstract

Spatially-resolved transcriptomics is revolutionizing our understanding of complex tissues, but their current use for the exploration of a few sections is not representative of their 3-dimensional architecture. In this work we present a low-cost strategy for manufacturing molecularly double-barcoded DNA arrays, enabling large-scale spatially-resolved transcriptomics studies. We applied this technique to spatially resolve gene expression in several human brain organoids, including the reconstruction of a 3-dimensional view from multiple consecutive sections, revealing gene expression divergencies throughout the tissue.

Complex In Vitro Model Characterization for Context of Use in Toxicologic Pathology: Use Cases by Collaborative Teams of Biologists, Bioengineers, and Pathologists

“…50 Moreover, spatial transcriptomics data from consecutive sections have been integrated to reconstruct a 3D molecular cartography of human brain organoids. 41 These studies and recent reviews underline the potential of combining single cell and spatial transcriptomics data to locate different cell types in organoids and to assess their molecular states. 35,62 Pathologists can support tissue preparation and guide the association of transcriptomic and morphological features, which will support validation and efficient application of these complex methods for CIVM characterization and toxicology readouts.…”

Untangling heterogeneity: From complexity to prediction

“…6 The costs of spatial genomics may fall for example through the development of novel bar-coding strategies, as exemplified by a recent study that used such a method to create a three-dimensional view of gene expression by profiling consecutive organoid sections. 7 The field will also need to expand analysis beyond areas of defined as cancerous by histopathology. For example, recent work identified copy-number instability in areas of prostate tissue that are histo-pathologically benign.…”