Identification of a murine CD45-F4/80lo HSC-derived marrow endosteal cell associated with donor stem cell engraftment

Hematopoietic stem cells (HSCs) reside in specialized microenvironments within the marrow designated as stem cell niches, which function to support HSCs at homeostasis and promote HSC engraftment after radioablation. We previously identified marrow space remodeling after hematopoietic ablation, including osteoblast thickening, osteoblast proliferation, and megakaryocyte migration to the endosteum, which is critical for effective engraftment of donor HSCs. To further evaluate the impact of hematopoietic cells on marrow remodeling, we used a transgenic mouse model (CD45Cre/iDTR) to selectively deplete hematopoietic cells in situ. Depletion of hematopoietic cells immediately before radioablation and hematopoietic stem cell transplantation abrogated donor HSC engraftment and was associated with strikingly flattened endosteal osteoblasts with preserved osteoblast proliferation and megakaryocyte migration. Depletion of monocytes, macrophages, or megakaryocytes (the predominant hematopoietic cell populations that survive short-term after irradiation) did not lead to an alteration of osteoblast morphology, suggesting that a hematopoietic-derived cell outside these lineages regulates osteoblast morphologic adaptation after irradiation. Using 2 lineage-tracing strategies, we identified a novel CD45-F4/80lo HSC-derived cell that resides among osteoblasts along the endosteal marrow surface and, at least transiently, survives radioablation. This newly identified marrow cell may be an important regulator of HSC engraftment, possibly by influencing the shape and function of endosteal osteoblasts

L'exposition "Sols fertiles, vies secrètes" du Sénat, ses panneaux de sensibilisation, leurs déclinaisons, leur diffusion et leurs impacts

International audienceThis paper deals with an exhibition: “Fertile soils and secret lives” designed at the initiative of Senat to raise public awareness of the soil resources knowledge and preservation issues. Exhibited for the first time in the Orangeries of the Luxembourg gardens in 2014,its design and diffusion involved the collaboration of numerous organizations, among which the French Soil Science Society. This very diverse exhibition attracted a very large and diverse public, with an estimated 50,000 persons involved between September 2014 and December 2019. The pedagogic posters designed on this occasion were further enriched, thanks to a collaboration with the CESE (Economic, Social and Environmental Council), with complementary posters about the links between soils and climate change. Then, they have been made available by the senate to AFES and declined in various formats (roll-ups, posters…) and presented in very numerous events (scientific congress of soil science, World Soil Day in France, open doors of agricultural high schools, libraries, …) to a very diverse public including professionals, students, general public and policy-makers. In this paper, we describe their dissemination and impact. These posters are still, and will be again, used. They are very good means to discover soils and to raise awareness about the major issues and challenges to which they contribute.Cet article présente une exposition, "Sols fertiles, vies secrètes", conçue à l'initiative du Sénat pour sensibiliser le grand public aux enjeux de la connaissance et de la préservation de nos ressources en sol. Exposée pour la première fois dans l'Orangerie des jardins du Luxembourg en 2014, sa conception et sa diffusion a mis à contribution de nombreux organismes, dont l'Association Française pour l'Etude du Sol. Cette exposition d'une grande diversité a touché un public nombreux et très divers avec selon nos estimations plus de 50 000 personnes touchées entre septembre 2014 et décembre 2019. Des panneaux pédagogiques ont été réalisés à cette occasion puis ont ensuite été enrichis grâce à une collaboration avec le CESE par des panneaux complémentaires sur le lien entre le sol et le climat. Ils ont été mis à disposition par le Sénat à l'AFES pour être déclinés sous différentes formes (roll-ups, affiches...) et présentés en de très nombreuses occasions (colloques de sciences du sol, Journée Mondiales des Sols, portes ouvertes de lycées agricoles, bibliothèques, …), en touchant un public varié (professionnels, étudiants, grand public, élus…). Nous décrivons ici leur diffusion et leur impact. Ces panneaux continuent, et continueront, d'être utilisés et constituent un excellent moyen de découverte des sols et de sensibilisation aux grands enjeux auxquels ils contribuent

Communiquer et sensibiliser le grand public aux sols

Cet article présente une exposition, "Sols fertiles, vies secrètes", conçue à l'initiative du Sénat pour sensibiliser le grand public aux enjeux de la connaissance et de la préservation de nos ressources en sol. Exposée pour la première fois dans l'Orangerie des jardins du Luxembourg en 2014, sa conception et sa diffusion a mis à contribution de nombreux organismes, dont l'Association Française pour l'Etude du Sol. Cette exposition d'une grande diversité a touché un public nombreux et très divers avec selon nos estimations plus de 50 000 personnes touchées entre septembre 2014 et décembre 2019. Des panneaux pédagogiques ont été réalisés à cette occasion puis ont ensuite été enrichis grâce à une collaboration avec le CESE par des panneaux complémentaires sur le lien entre le sol et le climat. Ils ont été mis à disposition par le Sénat à l'AFES pour être déclinés sous différentes formes (roll-ups, affiches...) et présentés en de très nombreuses occasions (colloques de sciences du sol, Journée Mondiales des Sols, portes ouvertes de lycées agricoles, bibliothèques, …), en touchant un public varié (professionnels, étudiants, grand public, élus…). Nous décrivons ici leur diffusion et leur impact. Ces panneaux continuent, et continueront, d'être utilisés et constituent un excellent moyen de découverte des sols et de sensibilisation aux grands enjeux auxquels ils contribuent

Splenic macrophage phagocytosis of intravenously infused mesenchymal stromal cells attenuates tumor localization

Mesenchymal stromal cells (MSCs) possess remarkable tumor tropism, making them ideal vehicles to deliver tumor-targeted therapeutic agents; however, their value in clinical medicine has yet to be realized. A barrier to clinical utilization is that only a small fraction of infused MSCs ultimately localize to the tumor. In an effort to overcome this obstacle, we sought to enhance MSC trafficking by focusing on the factors that govern MSC arrival within the tumor microenvironment. Our findings show that MSC chemoattraction is only present in select tumors, including osteosarcoma, and that the chemotactic potency among similar tumors varies substantially. Using an osteosarcoma xenograft model, we show that human MSCs traffic to the tumor within several hours of infusion. After arrival, MSCs are observed to localize in clusters near blood vessels and MSC-associated bioluminescence signal intensity is increased, suggesting that the seeded cells expand after engraftment. However, our studies reveal that a significant portion of MSCs are eliminated en route by splenic macrophage phagocytosis, effectively limiting the number of cells available for tumor engraftment. To increase MSC survival, we transiently depleted macrophages with liposomal clodronate, which resulted in increased tumor localization without substantial reduction in tumor-associated macrophages. Our data suggest that transient macrophage depletion will significantly increase the number of MSCs in the spleen and thus improve MSC localization within a tumor, theoretically increasing the effective dose of an anti-cancer agent. This strategy may subsequently improve the clinical efficacy of MSCs as vehicles for the tumor-directed delivery of therapeutic agents

Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling

Dynamin superfamily molecular motors use guanosine triphosphate (GTP) as a source of energy for membrane-remodeling events. We found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine triphosphate (ATP)–driven conversion of guanosine diphosphate (GDP), inhibited dynamin-mediated endocytosis. NM23-H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin. In vitro, NM23-H1/H2 were recruited to dynamin-induced tubules, stimulated GTP-loading on dynamin, and triggered fission in the presence of ATP and GDP. NM23-H4, a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 involved in mitochondria inner membrane fusion and increased GTP-loading on OPA1. Like OPA1 loss of function, silencing of NM23-H4 but not NM23-H1/H2 resulted in mitochondrial fragmentation, reflecting fusion defects. Thus, NDPKs interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency

NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy

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