Spatial Mapping of Thymic Stromal Microenvironments Reveals Unique Features Influencing T Lymphoid Differentiation

Interaction of hematopoietic progenitors with the thymic microenvironment induces them to proliferate, adopt the T lineage fate, and asymmetrically diverge into multiple functional lineages. Progenitors at various developmental stages are stratified within the thymus, implying that the corresponding microenvironments provide distinct sets of signals to progenitors migrating between them. These differences remain largely undefined. Here we used physical and computational approaches to generate a comprehensive spatial map of stromal gene expression in the thymus. Although most stromal regions were characterized by a unique gene expression signature, the central cortex lacked distinctive features. Instead, a key function of this region appears to be the sequestration of unique microenvironments found at the cortical extremities, thus modulating the relative proximity of progenitors moving between them. Our findings compel reexamination of how cell migration, lineage specification, and proliferation are controlled by thymic architecture and provide an in-depth resource for global characterization of this control.