Single-cell spatial mapping reveals reproducible cell type organization and spatially dependent gene expression in gastruloids

Gastruloids, stem-cell-based models that mirror essential features of mammalian gastrulation, including the formation of an anterior-posterior axis, remain understudied in terms of spatial information about gene expression and cell type organization. A recent study presents a comprehensive, single-cell molecular analysis of 26 individual gastruloids, revealing a consistent cell type composition and tissue-scale spatial arrangement across samples, yet notable variations in meso-scale patterning of specific cell types.

The researchers identified posterior cell types forming distinct, organized clusters, while anterior cell types exhibited a more disorganized spatial arrangement. To differentiate progressive differentiation from mere cell type diversity, the team introduced the L-score, a parameter-free method to quantify mutually exclusive gene expression.

This approach unveiled spatial organization without explicit encoding, mirrored known cell type relationships, and uncovered novel gene expression states and spatial subclusters within cell types.

The study confirmed that neuromesodermal precursor differentiation in gastruloids occurs through a continuous, spatially coordinated process. Furthermore, it demonstrated that endothelial precursors possess unique spatial organization and gene expression profiles contingent on their connection to either anterior somitic or posterior endodermal tissues.

This research not only lays the groundwork for utilizing gastruloids as robust models to investigate the molecular underpinnings of mammalian development and tissue organization but also introduces innovative computational tools for analyzing spatially resolved single-cell datasets.