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

Item Type:Article
Title:Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization
Creators: Baccin, C. ORCID logoORCID: https://orcid.org/0000-0003-1251-6947, Al-Sabah, J. ORCID logoORCID: https://orcid.org/0000-0003-2635-0423, Velten, L. ORCID logoORCID: https://orcid.org/0000-0002-1233-5874, Helbling, P.M. ORCID logoORCID: https://orcid.org/0000-0001-6488-2805, Grünschläger, F. ORCID logoORCID: https://orcid.org/0000-0003-0021-6912, Hernández-Malmierca, P. ORCID logoORCID: https://orcid.org/0000-0003-4529-384X, Nombela-Arrieta, C. ORCID logoORCID: https://orcid.org/0000-0003-0415-259X, Steinmetz, L.M. ORCID logoORCID: https://orcid.org/0000-0002-3962-2865, Trumpp, A. ORCID logoORCID: https://orcid.org/0000-0002-6212-3466 and Haas, S. ORCID logoORCID: https://orcid.org/0000-0001-9227-2051
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.
Keywords:Bone Marrow, Bone Marrow Cells, Hematopoietic Stem Cells, Mesenchymal Stem Cells, Osteoblasts, Stem Cell Niche, Transcriptome, Animals
Source:Nature Cell Biology
ISSN:1465-7392
Publisher:Nature Publishing Group
Volume:22
Number:1
Page Range:38-48
Date:January 2020
Official Publication:https://doi.org/10.1038/s41556-019-0439-6
PubMed:View item in PubMed

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