Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells

2016 ◽  
Vol 33 (1) ◽  
pp. 179-186 ◽  
Author(s):  
Hasbullah Daud ◽  
Susan Browne ◽  
Rasoul Al-Majmaie ◽  
William Murphy ◽  
Mohamed Al-Rubeai
Keyword(s):  
Red Blood Cells ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Metabolic Profiling ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

scholarly journals Differential Effects of RASA3 Mutations on Hematopoiesis are Profoundly Influenced by Genetic Background and Molecular Variant

2020 ◽  
Author(s):  
Raymond F. Robledo ◽  
Steven L. Ciciotte ◽  
Joel H. Graber ◽  
Yue Zhao ◽  
Amy J. Lambert ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Blood Cells ◽  
Genetic Background ◽  
White Blood Cells ◽  
Independent Effect ◽  
Mouse Strains ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Blood Formation ◽  
Molecular Variant

AbstractStudies of the severely pancytopenic scat mouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survival in utero; germline deletion is lethal at E12.5-13.5 due to severe hemorrhage and decreased fetal liver erythropoiesis. Conditional deletion in hematopoietic stem and progenitor cells (HSPCs) using Vav-Cre recapitulates the null phenotype demonstrating that RASA3 is required at the stem and progenitor level to maintain blood vessel development and integrity and effective blood production. In adults, bone marrow blood cell production and spleen stress erythropoiesis are suppressed significantly upon induction of RASA3 deficiency, leading to pancytopenia and death within two weeks. Notably, RASA3 missense mutations in mouse models scat (G125V) and hlb381 (H794L) show dramatically different hematopoietic consequences specific to both genetic background and molecular variant. Global transcriptomic studies in scat suggest potential targets to ameliorate disease progression.Author SummaryHematopoiesis is the process by which blood cells are formed. The individual must have a normal complement of red blood cells to prevent anemia, platelets to control bleeding, and white blood cells to maintain immune functions. All blood cells are derived from hematopoietic stem cells that differentiate into progenitor cells that then develop into mature circulating cells. We studied several mouse strains carrying different mutations in RASA3. We show that RASA3 is required at the earliest stages of blood formation, the stem and progenitor cells, and that the complement of genes other than RASA3, or the genetic background of the mutant strain, profoundly alters the overall effect on blood formation. Further, the molecular nature of the mutation in RASA3 also has a profound and independent effect on overall blood formation. One strain, designated scat, suffers cyclic anemia characterized by severe anemic crisis episodes interspersed with remissions where the anemia significantly improves. Comparison of scat crisis and remission hematopoietic stem and progenitor cells reveals striking differences in gene expression. Analyses of these expression differences provide clues to processes that potentially drive improvement of anemia in scat and provide new avenues to pursue in future studies to identify novel therapeutics for anemia.

scholarly journals BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Wenwen Zhou ◽  
Qiuping He ◽  
Chunxia Zhang ◽  
Xin He ◽  
Zongbin Cui ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Hematopoietic Stem ◽  
Lysosomal Trafficking ◽  
Embryonic Lethal ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Lysosome Related Organelles

Notch signaling plays a crucial role in controling the proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related complex (BORC). Bloc1s2−/− mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation of bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking to control multiple stem and progenitor cell homeostasis in vertebrates.

scholarly journals Hematopoietic Stem Cell Dynamics are Regulated by Progenitor Demand: Lessons from a Quantitative Modeling Approach

2018 ◽  
Author(s):  
Markus Klose ◽  
Maria Carolina Florian ◽  
Hartmut Geiger ◽  
Ingmar Glauche
Keyword(s):  
Progenitor Cells ◽  
Cell Dynamics ◽  
Hematopoietic Stem ◽  
Modeling Approach ◽  
Hematopoietic Recovery ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Quantitative Understanding ◽  
Varying Demand ◽  
Prevailing View

AbstractThe prevailing view on murine hematopoiesis and on hematopoietic stem cells (HSC) in particular derives from experiments that are related to regeneration after irradiation and HSC transplantation. However, over the past years, different experimental techniques have been developed to investigate hematopoiesis under homeostatic conditions, thereby providing access to proliferation and differentiation rates of hematopoietic stem and progenitor cells in the unperturbed situation. Moreover, it has become clear that hematopoiesis undergoes distinct changes during aging with large effects on HSC abundance, lineage contribution, asymmetry of division and self-renewal potential. However, it is currently not fully resolved how stem and progenitor cells interact to respond to varying demands and how this balance is altered by an aging-induced shift in HSC polarity.Here, we present anin-silicomodel to investigate the dynamics of HSC response to varying demand. By introducing an internal feedback between stem and progenitor cells, the model is suited to consistently describe both hematopoietic homeostasis and regeneration, including the limited regulation of HSCs in the homeostatic situation. The model further explains the age-dependent increase in phenotypic HSCs as a consequence of the cells’ inability to preserve divisional asymmetry.Our model suggests a dynamically regulated population of intrinsically asymmetrically dividing HSCs as suitable control mechanism that adheres with many qualitative and quantitative findings on hematopoietic recovery after stress and aging. The modeling approach thereby illustrates how a mathematical formalism can support the conceptual and the quantitative understanding of regulatory principles in HSC biology.

scholarly journals Peripheral blood hematopoietic stem cells: Biology, apheresis collection and cryopreservation

2007 ◽  
Vol 60 (1-2) ◽  
pp. 42-47 ◽  
Author(s):  
Ivana Urosevic ◽  
Bela Balint ◽  
Stevan Popovic
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Cell Damage ◽  
Small Population ◽  
Minimal Cell ◽  
Hematopoietic Stem ◽  
Acute Infarction ◽  
Stem And Progenitor Cells ◽  
Processing And Storage

Introduction Hematopoiesis is a continuous, dynamic and highly complex process resulting in production of various mature blood cells from a small population of pluripotent stem and progenitor cells through diverse proliferative and differentiative events. Numerous studies have demonstrated that a complex network of interactive cytokines regulates the survival, maturation, and proliferation of hematopoietic stem and progenitor cells (HSPCs). Application of cell-mediated therapy Massive application of different cell-mediated therapeutic methods has resulted in an increased need for both specific HSPCs and operating procedures providing minimal cell damage during collection, processing and storage in a liquid or frozen state. Therefore, the basic aim of cell harvesting, selection, as well as cryopreservation is to minimize cell damage during these procedures. HSPCs are cells which exhibit extensive self-renewal and proliferative capacity, associated with the capacity to differentiate into all blood cells and other cell lineages (plasticity of HSPC). Thanks to these properties, stem cells can provide complete and permanent restoration of hematopoiesis, which is the basis for clinical employment of HSPC transplantation. In addition, totipotent stem cells can be used for the so called "cell-therapy" in different clinical settings (e.g. myocardial regeneration after acute infarction). Conclusion Despite the fact that HSPC transplantation is already in routine use, some questions related to the optimal blood progenitor/cell collection, selection, storage and clinical use are still unresolved. Therefore, this review only briefly discusses the therapeutic use of HSPCs in different clinical areas and focuses on the recommendations, as well as the specific transfusion policies related to HSPC collection, processing, and cryopreservation with an emphasis on quality control.

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