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César Nombela-Arrieta

Department of Medical Oncology and Hematology; University Hospital of Zurich

Zurich, Switzerland

16:35 - 17:05

Day 1 – February 5, 2025

Bone marrow (BM) tissues are the prime sites for hematopoietic cell production, long-term reservoirs for immunological memory and hubs in which bone metabolism is orchestrated. Aside from its hematopoietic compartment, the BM is comprised of a heterogeneous stromal fraction of endothelial, mesenchymal and neural cells, which beyond proving the necessary tissue infrastructure, play fundamental regulatory roles in fine-tuning hematopoietic cell production as well as during marrow regeneration post-myeloablative damage. Exchange of critical regulatory signals between stromal and hematopoietic cells has been proposed to take place in restricted spatial locations termed niches, which are formed by a defined set of cellular subsets arranged in specific configurations. In our research group, we pioneered a customized pipeline for 3D quantitative microscopy (3D-QM), which combines organ-wide, deep tissue imaging of optically cleared BM slices, with state-of-the-art computational methods, such as deep learning convolutional neural networks for image-based analysis and advanced spatial statistics. This approach affords novel insight on tissue organization with unprecedented resolution. By combining 3D-QM with information derived from single cell RNA-seq analysis, high-dimensional flow cytometry and advanced mouse models, we study the structural organization of marrow tissues in homeostasis and the perturbations arising during pathological conditions. In this presentation I will discuss ongoing projects related to the canonical assembly of stromal cells into complex multicellular networks, the distribution of hematopoietic stem cell niches, and the dynamics of BM tissue regeneration post-myeloablative stress.