This project aims to understand the signaling that allows peripheral derived macrophages to engraft the brain after bone marrow transplantation. Under normal physiology, the brain is impermeable to peripheral cell engraftment. Bone marrow transplantation uses busulfan, a myeloablative drug, to kill bone marrow stem cells prior to stem cell transplantation. We discovered this drug also slowly kills the brain’s resident macrophages, microglia, and over time their decline provides a niche for peripheral derived macrophages to engraft the brain. Our key question is what signaling causes the brain to suddenly become permissive to this engraftment. We will use Visium HD spatial transcriptomics on tissue at the moment of brain engraftment to compare between brain regions in the same section that are void of engraftment, regions that are in the process of engraftment and regions that have been engrafted by peripheral derived macrophages. Our hypothesis is that the void to engraftment edge will have localized signaling that promotes brain engraftment. This study could provide new drug targets to recruit peripheral cells in the brain without utilizing the high risk procedure of bone marrow transplantation.
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