Fate-mapping mice: new tools and technology for immune discovery

Fate-mapping mice have revealed the developmental origins of multiple types of immune cells. When combined with technologies such as single cell RNA sequencing (scRNAseq), multiphoton imaging, and multiparameter flow cytometry, fate-mapping mice can define novel cell populations. When used in the context of infection and cancer, fate-mapping mice can both aid in understanding immune cell responses and help uncover new putative therapeutic targets that are unique to cells of specific developmental origins. Emerging fate-mapping models take advantage of newer genetic tools, such as cellular barcoding and stochastic multicolor reporters, thus allowing further resolution of the dynamics of immune cell populations in mice. The fate-mapping mouse has become an essential tool in the immunologist’s toolbox. Although traditionally used by developmental biologists to trace the origins of cells, immunologists are turning to fate-mapping to better understand the development and function of immune cells. Thus, an expansion in the variety of fate-mapping mouse models has occurred to answer fundamental questions about the immune system. These models are also being combined with new genetic tools to study cancer, infection, and autoimmunity. In this review, we summarize different types of fate-mapping mice and describe emerging technologies that might allow immunologists to leverage this valuable tool and expand our functional knowledge of the immune system. The fate-mapping mouse has become an essential tool in the immunologist’s toolbox. Although traditionally used by developmental biologists to trace the origins of cells, immunologists are turning to fate-mapping to better understand the development and function of immune cells. Thus, an expansion in the variety of fate-mapping mouse models has occurred to answer fundamental questions about the immune system. These models are also being combined with new genetic tools to study cancer, infection, and autoimmunity. In this review, we summarize different types of fate-mapping mice and describe emerging technologies that might allow immunologists to leverage this valuable tool and expand our functional knowledge of the immune system. self-cleaving peptide sequences placed between genes of interest; used to generate individual, instead of fusion proteins. tissue-clearing method for 3D imaging of entire organs without sectioning. biochemical process that B cells undergo to produce higher affinity antibodies. high-throughput sequencing technique assessing chromatin accessibility. translation of two genes from one mRNA transcript. mouse model in which the immune compartment is reconstituted with donor mouse stem cells. immunotherapeutic drug targeting immune regulators (checkpoints). immobilized cell arrays for single cell analysis. reporter mouse stochastically expressing different fluorescent proteins. bacteriophage P1-derived site-specific DNA recombinase. regulation of gene expression without changing DNA sequence. ER triple mutant with high specificity for tamoxifen. method used to study how the origin of cells influences their trajectory. technique that rapidly analyzes cells for parameters such as size, granularity, and protein expression. self-organized map algorithm used on flow cytometry data. flanked by two loxP sequences. marking unique identifiers with short DNA sequences. location within a lymphoid organ follicle where high-affinity antibodies are produced by B cells. molecular chaperone aiding in protein folding. NKT cell lymphoid population recognizing specific lipids. excitation occurs in a plane perpendicular to the observational direction. DNA sequence that is a target for Cre. computer systems that learn and adapt by using algorithms to analyze data patterns. fusion protein of Cre flanked by two modified ER-binding domains. innate-like T cell bearing an invariant T cell receptor. using near-infrared light to excite fluorescent molecules with 2+ photons to image deep into animal tissue while minimizing damage. gene region allowing genetic insertion without transgene silencing or dysregulation of neighboring genes; in this review, this is different from transcriptionally permissive. translation of multiple genes from a single mRNA transcript. system whereby Cre drives the generation of unique genetic barcodes. functional imaging technique using radioactive substances. dynamic analysis ordering cells along a lineage based on gene expression profiles. immunosuppressive CD4+ T cells. high-throughput sequencing analyzing transcriptional profiles. permissive gene locus for ubiquitous expression. sequencing method merging scRNAseq and live cell imaging. average number of times nucleotides are read in high-throughput sequencing. high-throughput sequencing analyzing transcriptional profiles of individual cells. CD4+ T cells that aid B cell maturation. CD4+ T cells producing interleukin (IL)-17. statistical method for visualizing high-dimensional data. dimension reduction algorithm for high parameter data.