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

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

  • Baccin C Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
  • Al-Sabah J Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.
  • Velten L Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. lars.velten@embl.de.
  • Helbling PM Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland.
  • Grünschläger F Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.
  • Hernández-Malmierca P Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.
  • Nombela-Arrieta C Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland.
  • Steinmetz LM Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. larsms@embl.de.
  • Trumpp A Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. a.trumpp@dkfz-heidelberg.de.
  • Haas S Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. s.haas@dkfz-heidelberg.de.
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  • 2019-12-25
Published in:
  • Nature cell biology. - 2020
Animals
Bone Marrow
Bone Marrow Cells
Hematopoietic Stem Cells
Mesenchymal Stem Cells
Osteoblasts
Stem Cell Niche
Transcriptome
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/152282
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