Mesenchymal Cell Contributions to the Stem Cell Niche Youmna Kfoury, David T. Scadden  Cell Stem Cell  Volume 16, Issue 3, Pages 239-253 (March 2015) DOI: 10.1016/j.stem.2015.02.019 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 A Timeline Representation of Major Discoveries that Shaped Our Understanding of MSCs and the Hematopoietic Microenvironment The work of 19th and 20th century scientists such as Conheim and Maximov shaped the early hypothesis concerning the existence of a BM stem cell population that is different from the HSC and that might be involved in its regulation. The concept was subsequently refined by Schofield who hypothesized that the microenvironment in which HSCs reside regulates and preserves their activity. The existence of MSCs was proven through the work of Friedenstein, which was crucial in the development of long-term HSC culture protocols. It was only in the dawn of the 21st century that the existence of the hematopoietic microenvironment was independently demonstrated in vivo through the work of Calvi and Zhang. Since then, technological advances at the level of genetically engineered animals in addition to cell labeling and sorting are expanding our understanding of MSC phenotypic and functional heterogeneity. Cell Stem Cell 2015 16, 239-253DOI: (10.1016/j.stem.2015.02.019) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 2 MSC Populations and Their Lineage-Traced Progeny during the Development of the Mouse Limb Column 2: A schematic representation of the mouse limb and the different MSC populations through development up to 1 week after birth starting with mesenchymal condensations and going through vascularization, formation of the mineralized matrix, and the colonization by HSCs. Column 3: MSC populations that have been detected or traced through genetic labeling. Column 3: The period of chase after genetic labeling. Column 4: The progeny detected after the indicated chase time. Cell Stem Cell 2015 16, 239-253DOI: (10.1016/j.stem.2015.02.019) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 3 Murine MSC Ontogeny The distinct waves of murine MSCs through development and their contribution to bone homeostasis. The blue axis represents the developmental time points at which the different MSC populations have been first detected and traced. The red axis represents the developmental stages at which the indicated progeny of the traced populations has been detected. Cell Stem Cell 2015 16, 239-253DOI: (10.1016/j.stem.2015.02.019) Copyright © 2015 Elsevier Inc. Terms and Conditions