Helen and Robert Appel Alzheimer’s Disease Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States
Lay Kodama
Gladstone Institute of Neurological Diseases, San Francisco, United States; Helen and Robert Appel Alzheimer’s Disease Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States; Medical Scientist Training Program, University of California at San Francisco, San Francisco, United States
Peter Dongmin Sohn
Gladstone Institute of Neurological Diseases, San Francisco, United States
Man Ying Wong
Helen and Robert Appel Alzheimer’s Disease Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States
Gergey Alzaem Mousa
Helen and Robert Appel Alzheimer’s Disease Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States
Yungui Zhou
Gladstone Institute of Neurological Diseases, San Francisco, United States
Yaqiao Li
Gladstone Institute of Neurological Diseases, San Francisco, United States
Gladstone Institute of Neurological Diseases, San Francisco, United States; Helen and Robert Appel Alzheimer’s Disease Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
Microglia are the resident myeloid cells in the central nervous system (CNS). The majority of microglia rely on CSF1R signaling for survival. However, a small subset of microglia in mouse brains can survive without CSF1R signaling and reestablish the microglial homeostatic population after CSF1R signaling returns. Using single-cell transcriptomic analysis, we characterized the heterogeneous microglial populations under CSF1R inhibition, including microglia with reduced homeostatic markers and elevated markers of inflammatory chemokines and proliferation. Importantly, MAC2/Lgals3 was upregulated under CSF1R inhibition, and shared striking similarities with microglial progenitors in the yolk sac and immature microglia in early embryos. Lineage-tracing studies revealed that these MAC2+ cells were of microglial origin. MAC2+ microglia were also present in non-treated adult mouse brains and exhibited immature transcriptomic signatures indistinguishable from those that survived CSF1R inhibition, supporting the notion that MAC2+ progenitor-like cells are present among adult microglia.
