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Fibroblastic reticular cells (FRCs) are specialized stromal cells of lymphoid organs that generate the structural foundation of the tissue and actively interact with immune cells. Distinct FRC subsets position lymphocytes and myeloid cells in specialized niches where they present processed or native antigen and provide essential growth factors and cytokines for immune cell activation and differentiation. Niche‐specific functions of FRC subpopulations have been defined using genetic targeting, high‐dimensional transcriptomic analyses, and advanced imaging methods. Here, we review recent findings on FRC‐immune cell interaction and the elaboration of FRC development and differentiation. We discuss how imaging approaches have not only shaped our understanding of FRC biology, but have critically advanced the niche concept of immune cell maintenance and control of immune reactivity. [ABSTRACT FROM AUTHOR]

Secondary lymphoid organs (SLO) are underpinned by fibroblastic reticular cells (FRC) that form dedicated microenvironmental niches to secure induction and regulation of innate and adaptive immunity. Distinct FRC subsets are strategically positioned in SLOs to provide niche factors and govern efficient immune cell interaction. In recent years, the use of specialized mouse models in combination with single‐cell transcriptomics has facilitated the elaboration of the molecular FRC landscape at an unprecedented resolution. While single‐cell RNA‐sequencing has advanced the resolution of FRC subset characterization and function, the high dimensionality of the generated data necessitates careful analysis and validation. Here, we reviewed novel findings from high‐resolution transcriptomic analyses that refine our understanding of FRC differentiation and activation processes in the context of infection and inflammation. We further discuss concepts, strategies, and limitations for the analysis of single‐cell transcriptome data from FRCs and the wide‐ranging implications for our understanding of stromal cell biology. [ABSTRACT FROM AUTHOR]

Summary: Cortical pyramidal cells are generated locally, from pre-programmed progenitors, to form functionally distinct areas. By contrast, striatal projection neurons (SPNs) are generated remotely from a common source, undergo migration to form mosaics of striosomes and matrix, and become incorporated into functionally distinct sectors. Striatal circuits might thus have a unique logic of developmental organization, distinct from those of the neocortex. We explore this possibility in mice by mapping one set of SPNs, those in striosomes, with striatonigral projections to the dopamine-containing substantia nigra pars compacta (SNpc). Same-age SPNs exhibit topographic striatonigral projections, according to their resident sector. However, the different birth dates of resident SPNs within a given sector specify the destination of their axons within the SNpc. These findings highlight a logic intercalating birth date-dependent and birth date-independent factors in determining the trajectories of SPN axons and organizing specialized units of striatonigral circuitry that could influence behavioral expression and vulnerabilities to disease.