The human bone marrow harbors a CD45(−) CD11B(+) cell progenitor permitting rapid microglia‐like cell derivative approaches

Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow‐derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia‐like cells to use in cell‐based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR‐MP). STR‐MP single‐cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial‐specific genes present in development and CNS pathologies. STR‐MPs can be expanded and generate microglia‐like cells in vitro, which we name stromal microglia (STR‐M). STR‐M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia‐like precursors that can be used in patient‐centered fast derivative approaches.