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

• DOI: 10.1038/s41467-018-04770-z
• Publication Date: 2018-06-22T14:07:35Z
• Authors: 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; César Nombela-Arr...
• Keywords: Aging; Statistical methods; Science; General Physics and Astronomy; 610 Medicine & health; 1600 General Chemistry; Genetics and Molecular Biology; Bone Marrow Cells; Cell Count; Article; Mice; Imaging, Three-Dimensional; Image processing; 1300 General Biochemistry, Genetics and Molecular Biology; Bone Marrow; Cell Movement; Animals; Femur; Stem Cell Niche; Microscopy; 10042 Clinic for Diagnostic and Interventional Radiology; Q; Endothelial Cells; Mesenchymal Stem Cells; General Chemistry; Hematopoietic Stem Cells; 3100 General Physics and Astronomy; Extracellular Matrix; Hematopoiesis; Mice, Inbred C57BL; Confocal microscopy; Haematopoiesis; Cellular Microenvironment; 10032 Clinic for Oncology and Hematology; General Biochemistry; Confocal microscopy; Haematopoiesis; Image processing; Statistical methods; Stem-cell niche; Stem-cell niche

AbstractSinusoidal 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.