The influence of environment and origin on brain resident macrophages and implications for therapy

Abstract

Microglia are the tissue-resident macrophages of the brain and spinal cord. They are critical players in the development, normal function, and decline of the CNS. Unlike traditional monocyte-derived macrophages, microglia originate from primitive hematopoiesis in the embryonic yolk sac and self-renew throughout life. Microglia also have a unique genetic signature among tissue resident macrophages. Recent studies identify the contributions of both brain environment and developmental history to the transcriptomic identity of microglia. Here we review this emerging literature and discuss the potential implications of origin on microglial function, with particular focus on existing and future therapies using bone-marrow- or stem-cell-derived cells for the treatment of neurological diseases.

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Fig. 1: Origin of microglia and microglia-like cells.
Fig. 2: The promise of microglia-based therapies.

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Acknowledgements

We thank the authors of the incredible works we’ve been lucky to read and attempt to honor in this manuscript; members of the Barres, Bennett, and Song-Ming labs, especially H. Song and G. Ming; members of our new clinical and research communities; and our discerning proofreaders K. Guttenplan, K. Nemec, D. Marzan, D. Barber, and A. Eisch.

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M.L.B. and F.C.B. were equal contributors to the conception and writing of this review.

Correspondence to Mariko L. Bennett.

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M.L.B and F.C.B are co-inventors on a pending patent filed by The Board of Trustees of The Leland Stanford Junior University (application 16/566,675) related to methods of microglia replacement.

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Bennett, M.L., Bennett, F.C. The influence of environment and origin on brain resident macrophages and implications for therapy. Nat Neurosci (2019) doi:10.1038/s41593-019-0545-6

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