Video legend. 3D Rendering of a Large Volume of the Femoral Diaphysis after induction of Chronic Myeloid Leukemia . The video sequentially shows the quantitative cellular analysis of MSCs and the co-localization of c-Kit+ cells in the vicinity and inside CML-induced MSC clusters. Prrx1-Cre+ tdTomato cells are shown in green and segmented cells in blue, while staining for c-Kit is depicted in magenta and segmentation of c-Kit+ cells are shown in multiple colors.
Cell Stem Cell 2019 March 21. doi.org/10.1016/j.stem.2019.02.018
Puneet Agarwal, Stephan Isringhausen, Hui Li, Andrew J. Paterson, Jianbo He, A lvaro Gomariz, Takashi Nagasawa, Cesar Nombela-Arrieta, and Ravi Bhatia
QUANTITATIVE SPATIAL ANALYSIS OF HEMATOPOIESIS-REGULATING STROMAL CELLS IN THE BONE MAROW MICROENVIRONMENT BY 3D MICROSCOPY
Nat Commun. 2018 Jun 28;9(1):2532.
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 conven- tional 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.
PATHOGEN-INDUCED TLR4-TRIF INNATE IMMUNE SIGNALING IN HEMATOPOIETIC STEM CELLS PROMOTES PROLIFERATION BUT REDUCES COMPETITIVE FITNESS
Cell Stem Cell. 2017 Aug 3;21(2):225-240.e5. doi: 10.1016/j.stem.2017.06.013
Takizawa H, Fritsch K, Kovtonyuk LV, Saito Y, Yakkala C, Jacobs K, Ahuja AK, Lopes M, Hausmann A, Hardt WD, Gomariz Á, Nombela-Arrieta C, Manz MG
DIFFERENTIAL REQUIREMENTS FOR DOCK2 AND PHOSPHOINOSITIDE-3-KINASE GAMMA DURING T AND B LYMPHOCYTE HOMING
Immunity. 2004 Sep;21(3):429-41.
Nombela-Arrieta C, Lacalle RA, Montoya MC, Kunisaki Y, Megías D, Marqués M, Carrera AC, Mañes S, Fukui Y, Martínez-A C, Stein JV.