Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging

Area of Science:

• Hematology
• Cell Biology
• Genomics
• Spatial Biology

Background:

• Non-hematopoietic cells are crucial for blood formation (hematopoiesis).
• Their diversity and spatial arrangement in human bone marrow are poorly understood.
• Understanding these cells is key to deciphering hematopoiesis.

Purpose of the Study:

• To characterize the heterogeneity and spatial organization of non-hematopoietic cells in human bone marrow.
• To map cellular interactions influencing hematopoiesis.
• To identify spatial alterations in bone marrow associated with acute myeloid leukemia (AML).

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to profile non-hematopoietic and hematopoietic cells.
• Co-detection by indexing (CODEX) for spatial profiling of over 1.2 million cells.
• Integration of scRNA-seq and CODEX data to link signaling with spatial proximity.

Main Results:

• Identified nine distinct subtypes of non-hematopoietic cells.
• Revealed a hyperoxygenated arterio-endosteal niche for early myelopoiesis.
• Discovered adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs).
• Uncovered mesenchymal stromal cell (MSC) expansion and specific spatial neighborhoods in AML patient samples.

Conclusions:

• Developed a spatially resolved, multiomic atlas of human bone marrow.
• This atlas serves as a reference for studying cellular interactions in hematopoiesis.
• Identified distinct cellular niches and spatial alterations in AML, highlighting the role of MSCs.