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Nature cell biology
01, 2020;22 (1): 38-48.

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

Chiara Baccin, Jude Al-Sabah, Lars Velten, Patrick M Helbling, Florian Grünschläger, Pablo Hernández-Malmierca, César Nombela-Arrieta, Lars M Steinmetz, Andreas Trumpp, Simon Haas
Author Information
  1. Chiara Baccin: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. ORCID
  2. Jude Al-Sabah: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. ORCID
  3. Lars Velten: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. lars.velten@embl.de. ORCID
  4. Patrick M Helbling: Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland. ORCID
  5. Florian Grünschläger: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. ORCID
  6. Pablo Hernández-Malmierca: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. ORCID
  7. César Nombela-Arrieta: Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland. ORCID
  8. Lars M Steinmetz: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. larsms@embl.de. ORCID
  9. Andreas Trumpp: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. a.trumpp@dkfz-heidelberg.de. ORCID
  10. Simon Haas: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. s.haas@dkfz-heidelberg.de. ORCID
PMID: 31871321 DOI: 10.1038/s41556-019-0439-6

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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Grants

  1. 294542/European Research Council
  2. 742804/European Research Council
  3. P01 AG020752/NIA NIH HHS

MeSH Term

Animals
Bone Marrow
Bone Marrow Cells
Hematopoietic Stem Cells
Mesenchymal Stem Cells
Osteoblasts
Stem Cell Niche
Transcriptome
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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