Journal
NATURE CELL BIOLOGY
Volume 22, Issue 1, Pages 38-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41556-019-0439-6
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SFB873, FOR2674, FOR2033]
- SyTASC consortium (Deutsche Krebshilfe)
- Dietmar Hopp Foundation
- US National Institutes of Health [P01HG00020527]
- ERC [742804]
- Jose Carreras Foundation for Leukemia Research [DCJLS 20R/2017]
- European Research Council (ERC) [742804] Funding Source: European Research Council (ERC)
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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.
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