Cellular and structural dynamics of the bone marrow stromal microenvironment in homeostasis and inflammation

Date

Mar 16, 2017

Time

2:30 PM - 3:30 PM

Speaker

Prof. César Nombela-Arrieta (PhD)

Affiliation

University Hospital Zurich, Department of Experimental Hematology

Series

IMB - Seminar

Language

en

Main Topic

Biologie

Other Topics

Biologie, Medizin

Host

IMB

Description

During adulthood, bone marrow (BM) cavities are the primary sites of production of vast amounts of blood cellular components from a rare population of hematopoietic stem cells (HSCs). Beyond their hematopoietic function, BM tissues host immune responses and maintain immunological memory. Aside from its hematopoietic compartment, the BM is comprised of a heterogeneous stromal fraction of endothelial, mesenchymal and neural cells, which play essential regulatory roles and provide the necessary infrastructure for hematopoiesis to unfold. A thorough understanding of the spatial distributions, structural dynamics and interactions established by diverse cellular components within the complex landscape of the BM is key for the generation of comprehensive models of healthy and pathological hematopoiesis. We have recently developed advanced microscopy protocols that enable the 3D visualization of large volumes of BM tissues at an organ-wide level with cellular and subcellular resolution. When combined with customized computational tools, these techniques generate quantitative spatial information in an automatic and unbiased fashion and enable the extraction of positional statistics for rigorous analysis of cellular interactions. Using these tools we provide a detailed overview of the distribution, topology and spatial relationships of mesenchymal stromal cells as well as sinusoidal microvessels, two essential regulatory components of HSC niches. Our analyses indicate that both stromal cell networks largely pervade BM cavities and strictly limit the 3D tissue space available for hematopoiesis. Finally, we employ these unique methods to investigate the dynamic structural alterations induced by chronic infections in BM stromal integrity.

Last modified: Feb 21, 2017, 2:32:10 PM