Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and 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 used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. 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…

• CH
  Children's Hospital of Philadelphia
• UO
  University of Pennsylvania
• RP
  Regeneron Pharmaceuticals
• NI
  National Institutes of Health

  Awards: P30AR069619, T32 GM007170, HL156090, T32 HL007439, U2C CA233285, T32DK007314, R01AG069401, CA233285
• G
  Genentech
• NO
  NIH Office of the Director

  Award: P30AR069619
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: T32 GM007170, T32 HL007439, T32DK007314, F30CA277965
• OO
  Office of Strategic Coordination
• JP
  Janssen Pharmaceuticals
• CF
  Common Fund