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

Nat Cell Biol. 2020 Jan;22(1):38-48. doi: 10.1038/s41556-019-0439-6. Epub 2019 Dec 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / metabolism*
  • Bone Marrow Cells / metabolism*
  • Hematopoietic Stem Cells / metabolism*
  • Mesenchymal Stem Cells / metabolism
  • Osteoblasts / metabolism
  • Stem Cell Niche / physiology
  • Transcriptome / physiology*