Quantitative spatial analysis of haematopoiesis-regulating stromal cells in the bone marrow microenvironment by 3D microscopy

Nat Commun. 2018 Jun 28;9(1):2532. doi: 10.1038/s41467-018-04770-z.


Sinusoidal endothelial cells and mesenchymal CXCL12-abundant reticular cells are principal bone marrow stromal components, which critically modulate haematopoiesis at various levels, including haematopoietic stem cell maintenance. These stromal subsets are thought to be scarce and function via highly specific interactions in anatomically confined niches. Yet, knowledge on their abundance, global distribution and spatial associations remains limited. Using three-dimensional quantitative microscopy we show that sinusoidal endothelial and mesenchymal reticular subsets are remarkably more abundant than estimated by conventional flow cytometry. Moreover, both cell types assemble in topologically complex networks, associate to extracellular matrix and pervade marrow tissues. Through spatial statistical methods we challenge previous models and demonstrate that even in the absence of major specific interaction forces, virtually all tissue-resident cells are invariably in physical contact with, or close proximity to, mesenchymal reticular and sinusoidal endothelial cells. We further show that basic structural features of these stromal components are preserved during ageing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Bone Marrow / diagnostic imaging
  • Bone Marrow / physiology
  • Bone Marrow Cells / physiology
  • Bone Marrow Cells / ultrastructure*
  • Cell Count
  • Cell Movement
  • Cellular Microenvironment / physiology
  • Endothelial Cells / physiology
  • Endothelial Cells / ultrastructure
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / ultrastructure
  • Femur / cytology*
  • Femur / diagnostic imaging
  • Femur / physiology
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / physiology
  • Hematopoietic Stem Cells / ultrastructure*
  • Imaging, Three-Dimensional / statistics & numerical data
  • Mesenchymal Stem Cells / physiology
  • Mesenchymal Stem Cells / ultrastructure*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy / methods
  • Stem Cell Niche