Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Proteomic Imaging

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We employed Co-Detection by Indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-Seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells. We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in AML patient samples. This spatially-resolved, multiomic atlas of human bone marrow will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.