scholarly journals Human hematopoietic stem/progenitor cells display reactive oxygen species-dependent long-term hematopoietic defects after exposure to low doses of ionizing radiations

Haematologica ◽  
2019 ◽  
Vol 105 (8) ◽  
pp. 2044-2055 ◽  
Author(s):  
Elia Henry ◽  
Inès Souissi-Sahraoui ◽  
Margaux Deynoux ◽  
Andréas Lefèvre ◽  
Vilma Barroca ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Progenitor Cells ◽  
Reactive Oxygen ◽  
Low Doses ◽  
Oxygen Species ◽  
Hematopoietic Stem ◽  
Ionizing Radiations

scholarly journals Microwaves from mobile phone induce reactive oxygen species but not DNA damage, preleukemic fusion genes and apoptosis in hematopoietic stem/progenitor cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matus Durdik ◽  
Pavol Kosik ◽  
Eva Markova ◽  
Alexandra Somsedikova ◽  
Beata Gajdosechova ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Mobile Phone ◽  
Progenitor Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Fusion Genes ◽  
Microscopy Imaging ◽  
Hematopoietic Stem

Abstract Exposure to electromagnetic fields (EMF) has been associated with the increased risk of childhood leukemia, which arises from mutations induced within hematopoietic stem cells often through preleukemic fusion genes (PFG). In this study we investigated whether exposure to microwaves (MW) emitted by mobile phones could induce various biochemical markers of cellular damage including reactive oxygen species (ROS), DNA single and double strand breaks, PFG, and apoptosis in umbilical cord blood (UCB) cells including CD34+ hematopoietic stem/progenitor cells. UCB cells were exposed to MW pulsed signals from GSM900/UMTS test-mobile phone and ROS, apoptosis, DNA damage, and PFG were analyzed using flow cytometry, automated fluorescent microscopy, imaging flow cytometry, comet assay, and RT-qPCR. In general, no persisting difference in DNA damage, PFG and apoptosis between exposed and sham-exposed samples was detected. However, we found increased ROS level after 1 h of UMTS exposure that was not evident 3 h post-exposure. We also found that the level of ROS rise with the higher degree of cellular differentiation. Our data show that UCB cells exposed to pulsed MW developed transient increase in ROS that did not result in sustained DNA damage and apoptosis.

FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulation

Blood ◽  
2012 ◽  
Vol 120 (9) ◽  
pp. 1843-1855 ◽  
Author(s):  
Tomer Itkin ◽  
Aya Ludin ◽  
Ben Gradus ◽  
Shiri Gur-Cohen ◽  
Alexander Kalinkovich ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Reactive Oxygen ◽  
Receptor Activation ◽  
Oxygen Species ◽  
Hematopoietic Stem ◽  
Cell Engraftment ◽  
Stem And Progenitor Cells

Abstract Cytokine-induced expansion of hematopoietic stem and progenitor cells (HSPCs) is not fully understood. In the present study, we show that whereas steady-state hematopoiesis is normal in basic fibroblast growth factor (FGF-2)–knockout mice, parathyroid hormone stimulation and myeloablative treatments failed to induce normal HSPC proliferation and recovery. In vivo FGF-2 treatment expanded stromal cells, including perivascular Nestin+ supportive stromal cells, which may facilitate HSPC expansion by increasing SCF and reducing CXCL12 via mir-31 up-regulation. FGF-2 predominantly expanded a heterogeneous population of undifferentiated HSPCs, preserving and increasing durable short- and long-term repopulation potential. Mechanistically, these effects were mediated by c-Kit receptor activation, STAT5 phosphorylation, and reduction of reactive oxygen species levels. Mice harboring defective c-Kit signaling exhibited abrogated HSPC expansion in response to FGF-2 treatment, which was accompanied by elevated reactive oxygen species levels. The results of the present study reveal a novel mechanism underlying FGF-2–mediated in vivo expansion of both HSPCs and their supportive stromal cells, which may be used to improve stem cell engraftment after clinical transplantation.

Loss of Foxo3a In FA Mice Leads to Hematopoietic Stem Cell Exhaustion That Can Be Attenuated by Natural Anti-Oxidant Quercetin.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1166-1166
Author(s):  
Jie Li ◽  
Jared Sipple ◽  
Qishen Pang
Keyword(s):  
Reactive Oxygen Species ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Genetic Disorder ◽  
Specific Interaction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hematopoietic Stem ◽  
Anti Oxidant

Abstract Abstract 1166 Fanconi anemia (FA) is a genetic disorder characterized by genomic instability, bone marrow (BM) failure and predisposition to cancer. However, FA mouse models do not show spontaneous genetic instability. Previous study shows that FOXO3a is associated with the FA pathway through oxidative stress-specific interaction with FANCD2. To address the consequence of loss of FOXO3a function in FA hematopoiesis, we generated Foxo3a-/-Fancd2-/- and Foxo3a-/-Fancc-/- double-knockout (DKO) mice by crossing Foxo3a+/− with Fancd2+/− or Fancc+/−; mice. Reactive oxygen species are increased in low-density BM (LDBM) cells isolated from DKO mice compared to those from single KO (SKO) or wt mice. Analysis of hematologic parameters shows significantly increased number of nucleate cells and high ratio of eosinophils in peripheral blood of DKO mice. CFU assay shows more progenitor cells in peripheral blood isolated from DKO mice. Moreover, BM progenitor cells from DKO mice exhibit lower adhesion but higher migration activity, compared to those from wt or SKO mice. Consistent with this, Cdc42 pull-down assay shows lower Cdc42 activity in DKO LDBM cells than in wt or SKO cells, indicating that decreased Cdc42 may contribute to the observed aberrant adhesion and migration activities. DKO mice show significant decrease in primitive progenitor (Lin-Sca-1+c-kit+; LSK) cells, increase in BrdU+ and G1-phase LSK cells, and impaired repopulating capacity after competitive BM transplantation, which can be attenuated by the anti-oxidant Quercetin. Taken together, loss of Foxo3a in FA mice results in FA-like syndrome, which may be resulted from increased reactive oxygen species accumulation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4030-4038 ◽  
Author(s):  
Marisa M. Juntilla ◽  
Vineet D. Patil ◽  
Marco Calamito ◽  
Rohan P. Joshi ◽  
Morris J. Birnbaum ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Function ◽  
Reactive Oxygen ◽  
Lymphoid Cells ◽  
Oxygen Species ◽  
Cellular Functions ◽  
Hematopoietic Stem ◽  
G0 Phase

Although AKT is essential for multiple cellular functions, the role of this kinase family in hematopoietic stem cells (HSCs) is unknown. Thus, we analyzed HSC function in mice deficient in the 2 isoforms most highly expressed in the hematopoietic compartment, AKT1 and AKT2. Although loss of either isoform had only a minimal effect on HSC function, AKT1/2 double-deficient HSCs competed poorly against wild-type cells in the development of myeloid and lymphoid cells in in vivo reconstitution assays. Serial transplantations revealed an essential role for AKT1 and AKT2 in the maintenance of long-term HSCs (LT-HSCs). AKT1/2 double-deficient LT-HSCs were found to persist in the G0 phase of the cell cycle, suggesting that the long-term functional defects are caused by increased quiescence. Furthermore, we found that the intracellular content of reactive oxygen species (ROS) is dependent on AKT because double-deficient HSCs demonstrate decreased ROS. The importance of maintaining ROS for HSC differentiation was shown by a rescue of the differentiation defect after pharmacologically increasing ROS levels in double-deficient HSCs. These data implicate AKT1 and AKT2 as critical regulators of LT-HSC function and suggest that defective ROS homeostasis may contribute to failed hematopoiesis.

scholarly journals Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress

Blood ◽  
2012 ◽  
Vol 120 (25) ◽  
pp. 4973-4981 ◽  
Author(s):  
Zeenath Unnisa ◽  
Jason P. Clark ◽  
Jayeeta Roychoudhury ◽  
Elizabeth Thomas ◽  
Lino Tessarollo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hematopoietic Stem ◽  
Knock Out ◽  
Von Hippel Lindau ◽  
Expression Of Genes

Abstract The transcription factor Meis1 is expressed preferentially in hematopoietic stem cells (HSCs) and overexpressed in certain leukemias. However, the functions of Meis1 in hematopoiesis remain largely unknown. In the present study, we found that Meis1 is required for the maintenance of hematopoiesis under stress and over the long term, whereas steady-state hematopoiesis was sustained in the absence of Meis1 in inducible knock-out mice. BM cells of Meis1-deficient mice showed reduced colony formation and contained significantly fewer numbers of long-term HSCs, which exhibited loss of quiescence. Further, we found that Meis1 deletion led to the accumulation of reactive oxygen species in HSCs and decreased expression of genes implicated in hypoxia response. Finally, reactive oxygen species scavenging by N-acetyl cysteine or stabilization of hypoxia signaling by knockdown of the von-Hippel-Lindau (VHL) protein led to reversal of the effects of Meis1 deletion. The results of the present study demonstrate that Meis1 protects and preserves HSCs by restricting oxidative metabolism.

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