Re-analysis of single-cell RNA-seq data provides insights into the roles of cycling myeloid cells in tissue repair

Abstract

Abstract As the resident macrophages in the central nervous system (CNS), microglial cells are responsible for the innate immunity of the brain and spinal cord. Based on many previous studies, it is well accepted that the large increase in microglia after CNS damage involves both the expansion of endogenous resident microglia and the acute, active recruitment of bone marrow–derived microglia progenitors. However, a comparatively new study has presented a different conclusion, stating that repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Cycling myeloid cells are often detected in a distinct cluster using single-cell RNA sequencing (scRNA-seq) datasets, however, they were not recognized for their research value before. By our analysis, cycling myeloid cells belong to a specific cell type, which serves as a direct progenitor population for differentiation into microglia. For the first time, these cells have been linked with microglia, monocytes, and macrophages, which is a pivotal step to reveal the mechanisms underlying microglia repopulation after CNS injury. The present study sets the stage for intensive studies on these cycling myeloid cells in the future, which have significant implications for the understanding of their origins and roles as the immune progenitor cells in various physiological and pathological processes, particularly those related to spinal cord injury and breast cancer, leading to develop targeted therapies or interventions.