Combined single-cell and spatial transcriptomics reveals the molecular, cellular and spatial bone marrow niche organization

By Chiara Baccin, Jude Al-Sabah, Lars Velten, Patrick M. Helbling, F. Grünschläger, Pablo Hernández-Malmierca, C. Nombela-Arrieta, Lars M. Steinmetz, A. Trumpp, S. Haas. Nature Cell Biology, 2019

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The bone marrow constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular and spatial organization remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular, cellular and spatial composition of distinct bone marrow niches. This allowed us to transcriptionally profile all major bone-marrow-resident cell types, determine their localization and clarify sources of pro-haematopoietic factors. Our data demonstrate that Cxcl12-abundant-reticular (CAR) cell subsets (Adipo-CAR and Osteo-CAR) differentially localize to sinusoidal and arteriolar surfaces, act locally as ‘professional cytokine-secreting cells’ and thereby establish peri-vascular micro-niches. Importantly, the three-dimensional bone-marrow organization can be accurately inferred from single-cell transcriptome data using the RNA-Magnet algorithm described here. Together, our study reveals the cellular and spatial organization of bone marrow niches and offers a systematic approach to dissect the complex organization of whole organs. Baccin, Al-Sabah, Velten et al. use single-cell and spatially resolved transcriptomics to map the cellular, molecular and spatial organization of the endosteal, sinusoidal and arteriolar bone marrow niches.

Subfields: Hematology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a39876c66cd652fbcf22bc84a2075980a5524c85