Modeling tissue-resident macrophage development from mouse pluripotent stem cells
Year: 2025
Type: preprint
Abstract: SUMMARY Tissue-resident macrophages (TRMs) are innate immune cells that participate in tissue development, homeostasis, and immune surveillance. Extensive efforts have been made to recapitulate TRM development from pluripotent stem cells (PSCs) in vitro to study molecular and cellular mechanisms of TRM development and to create cellular models of disease. However, available PSC models of mouse TRM development exhibit low overall efficiencies of TRM generation, produce heterogeneous off-target populations, and rely upon undefined media components, thus limiting their reproducibility, scalability, and widespread application as an experimental platform for TRM biology. To address these important limitations, we developed an efficient and reproducible protocol to faithfully recapitulate the stepwise differentiation of mouse PSCs (epiblast stem cells) into unspecialized, proliferative TRMs through the pro-definitive hematopoietic program under defined conditions. These immature TRMs can stably integrate into developing mouse neural organoids in vitro and acquire features of microglia. In addition, PSC-derived immature TRMs can stably engraft into the lung niche in vivo and adopt alveolar macrophage characteristics. This new platform for modeling mouse TRM development represents a powerful experimental model system for studying TRM function and dysfunction in development and disease.
Institutions: Memorial Sloan Kettering Cancer Center, Cornell University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Rethinking the "quiet" nature of apoptotic cell clearance., Regulation of tumor-associated phagocyte physiology during tumor cell clearance, The CSBC Research Center for Cancer Systems Immunology at MSKCC, WNK1-dependent macropinocytosis mediates emergency myelopoiesis, Cancer Center Support Grant
OpenAlex ID: W4410091558