nam 22 uu 4500 dbt_mods_00049438 10.3389/fcell.2021.705410 doi dbt_mods_00049438 ger DE-601 rda eng 570 sdnb Fröbel, Julia Author aut Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute The hematopoietic bone marrow niche ecosystem Fröbel, Julia;Landspersky, Theresa;Percin, Gülce;Schreck, Christina;Rahmig, Susann;Ori, Alessandro;Nowak, Daniel;Essers, Marieke;Waskow, Claudia;Oostendorp, Robert A. J. Lausanne Frontiers Media 2021-07-22 19 Seiten text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Zweitveröffentlichung The bone marrow (BM) microenvironment, also called the BM niche, is essential for the maintenance of fully functional blood cell formation (hematopoiesis) throughout life. Under physiologic conditions the niche protects hematopoietic stem cells (HSCs) from sustained or overstimulation. Acute or chronic stress deregulates hematopoiesis and some of these alterations occur indirectly via the niche. Effects on niche cells include skewing of its cellular composition, specific localization and molecular signals that differentially regulate the function of HSCs and their progeny. Importantly, while acute insults display only transient effects, repeated or chronic insults lead to sustained alterations of the niche, resulting in HSC deregulation. We here describe how changes in BM niche composition (ecosystem) and structure (remodeling) modulate activation of HSCs in situ . Current knowledge has revealed that upon chronic stimulation, BM remodeling is more extensive and otherwise quiescent HSCs may be lost due to diminished cellular maintenance processes, such as autophagy, ER stress response, and DNA repair. Features of aging in the BM ecology may be the consequence of intermittent stress responses, ultimately resulting in the degeneration of the supportive stem cell microenvironment. Both chronic stress and aging impair the functionality of HSCs and increase the overall susceptibility to development of diseases, including malignant transformation. To understand functional degeneration, an important prerequisite is to define distinguishing features of unperturbed niche homeostasis in different settings. A unique setting in this respect is xenotransplantation, in which human cells depend on niche factors produced by other species, some of which we will review. These insights should help to assess deviations from the steady state to actively protect and improve recovery of the niche ecosystem in situ to optimally sustain healthy hematopoiesis in experimental and clinical settings. niche microenvironment bone marrow hematopoiesis leukemia aging transplantation xenograft article Landspersky, Theresa Author aut School of Medicine, Department of Internal Medicine III, Technical University of Munich Percin, Gülce Author aut Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute Schreck, Christina Author aut School of Medicine, Department of Internal Medicine III, Technical University of Munich Rahmig, Susann Author aut Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute Ori, Alessandro Author aut Proteomics of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute Nowak, Daniel Author aut Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University Essers, Marieke Author aut Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ) Waskow, Claudia Author aut Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute Institute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich Schiller University Jena Department of Medicine III, Technical University Dresden Oostendorp, Robert A. J. Author aut School of Medicine, Department of Internal Medicine III, Technical University of Munich Friedrich-Schiller-Universität Jena Sonstige/Externe host institution his 9, 2021:705410<1 Front. Cell Dev. Biol. Frontiers in Cell and Developmental Biology 2296-634X dbt_mods_00049439 https://www.db-thueringen.de/receive/dbt_mods_00049438 object in context https://www.db-thueringen.de/servlets/MCRFileNodeServlet/dbt_derivate_00053962/fcell-09-705410.pdf raw object https://www.db-thueringen.de/rsc/thumbnail/dbt_mods_00049438.png preview https://www.db-thueringen.de/receive/dbt_mods_00049438 uri