The Hematopoietic Bone Marrow Niche Ecosystem
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 chro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.705410/full |
| _version_ | 1818647905425162240 |
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| author | Julia Fröbel Theresa Landspersky Gülce Percin Christina Schreck Susann Rahmig Alessandro Ori Daniel Nowak Marieke Essers Marieke Essers Claudia Waskow Claudia Waskow Claudia Waskow Robert A. J. Oostendorp |
| author_facet | Julia Fröbel Theresa Landspersky Gülce Percin Christina Schreck Susann Rahmig Alessandro Ori Daniel Nowak Marieke Essers Marieke Essers Claudia Waskow Claudia Waskow Claudia Waskow Robert A. J. Oostendorp |
| author_sort | Julia Fröbel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:09:57Z |
| format | Article |
| id | doaj.art-920b51b18108497895723e870741b699 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-17T01:09:57Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-920b51b18108497895723e870741b6992022-12-21T22:09:10ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.705410705410The Hematopoietic Bone Marrow Niche EcosystemJulia Fröbel0Theresa Landspersky1Gülce Percin2Christina Schreck3Susann Rahmig4Alessandro Ori5Daniel Nowak6Marieke Essers7Marieke Essers8Claudia Waskow9Claudia Waskow10Claudia Waskow11Robert A. J. Oostendorp12Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanySchool of Medicine, Department of Internal Medicine III, Technical University of Munich, Munich, GermanyImmunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanySchool of Medicine, Department of Internal Medicine III, Technical University of Munich, Munich, GermanyImmunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanyProteomics of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanyDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, GermanyHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, GermanyDivision Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), Heidelberg, GermanyImmunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanyInstitute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich Schiller University Jena, Jena, GermanyDepartment of Medicine III, Technical University Dresden, Dresden, GermanySchool of Medicine, Department of Internal Medicine III, Technical University of Munich, Munich, GermanyThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.705410/fullnichemicroenvironmentbone marrowhematopoiesisleukemiaaging |
| spellingShingle | Julia Fröbel Theresa Landspersky Gülce Percin Christina Schreck Susann Rahmig Alessandro Ori Daniel Nowak Marieke Essers Marieke Essers Claudia Waskow Claudia Waskow Claudia Waskow Robert A. J. Oostendorp The Hematopoietic Bone Marrow Niche Ecosystem Frontiers in Cell and Developmental Biology niche microenvironment bone marrow hematopoiesis leukemia aging |
| title | The Hematopoietic Bone Marrow Niche Ecosystem |
| title_full | The Hematopoietic Bone Marrow Niche Ecosystem |
| title_fullStr | The Hematopoietic Bone Marrow Niche Ecosystem |
| title_full_unstemmed | The Hematopoietic Bone Marrow Niche Ecosystem |
| title_short | The Hematopoietic Bone Marrow Niche Ecosystem |
| title_sort | hematopoietic bone marrow niche ecosystem |
| topic | niche microenvironment bone marrow hematopoiesis leukemia aging |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.705410/full |
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