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

C Baccin, J Al-Sabah, L Velten, PM Helbling… - Nature cell …, 2020 - nature.com
C Baccin, J Al-Sabah, L Velten, PM Helbling, F Grünschläger, P Hernández-Malmierca…
Nature cell biology, 2020nature.com
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 …
Abstract
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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