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

Alvaro Gomariz, Patrick M. Helbling, Stephan Isringhausen, Ute Suessbier, Anton Becker, Andreas Boss, Takashi Nagasawa, Grégory Paul, Orcun Goksel, Gábor Székely, Szymon Stoma, Simon F. Nørrelykke, Markus G. Manz and César Nombela-Arrieta ()
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Alvaro Gomariz: University Hospital and University of Zurich
Patrick M. Helbling: University Hospital and University of Zurich
Stephan Isringhausen: University Hospital and University of Zurich
Ute Suessbier: University Hospital and University of Zurich
Anton Becker: University Hospital Zurich
Andreas Boss: University Hospital Zurich
Takashi Nagasawa: Osaka University
Grégory Paul: ETH Zurich
Orcun Goksel: ETH Zurich
Gábor Székely: ETH Zurich
Szymon Stoma: ETH Zurich
Simon F. Nørrelykke: ETH Zurich
Markus G. Manz: University Hospital and University of Zurich
César Nombela-Arrieta: University Hospital and University of Zurich

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-04770-z

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