Abstract：
:Stem cells of highly regenerative organs including blood are susceptible to endogenous DNA damage caused by both intrinsic and extrinsic stress. Response mechanisms to such stress equipped in hematopoietic stem cells (HSCs) are crucial in sustaining hematopoietic homeostasis but remain largely unknown. In this study, we demonstrate that serial transplantation of human HSCs into immunodeficient mice triggers replication stress that induces incremental elevation of intracellular reactive oxygen species (ROS) levels and the accumulation of persistent DNA damage within the human HSCs. This accumulation of DNA damage is also detected in HSCs of clinical HSC transplant patients and elderly individuals. A forced increase of intracellular levels of ROS by treatment with a glutathione synthetase inhibitor aggravates the extent of DNA damage, resulting in the functional impairment of HSCs in vivo. The oxidative DNA damage activates the expression of cell-cycle inhibitors in a HSC specific manner, leading to the premature senescence among HSCs, and ultimately to the loss of stem cell function. Importantly, treatment with an antioxidant can antagonize the oxidative DNA damage and eventual HSC dysfunction. The study reveals that ROS play a causative role for DNA damage and the regulation of ROS have a major influence on human HSC aging.
journal_name
Bloodjournal_title
Bloodauthors
Yahata T,Takanashi T,Muguruma Y,Ibrahim AA,Matsuzawa H,Uno T,Sheng Y,Onizuka M,Ito M,Kato S,Ando Kdoi
10.1182/blood-2011-01-330050subject
Has Abstractpub_date
2011-09-15 00:00:00pages
2941-50issue
11eissn
0006-4971issn
1528-0020pii
blood-2011-01-330050journal_volume
118pub_type
杂志文章相关文献
BLOOD文献大全abstract：:CD34+ cells devoid of detectable mature and immature T and B lymphocytes, expressing the CD2, CD10, and CD20 antigens, were isolated from marrows of three pairs of sex-mismatched, mixed lymphocyte culture (MLC) nonreactive, sibling baboons. Reciprocal transplants were performed between members of each pair, using the ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:Platelets play a crucial role in the physiology of primary hemostasis and pathophysiologic processes such as arterial thrombosis. Accumulating evidence suggests a role of reactive oxygen species (ROSs) in platelet activation. Here we show that platelets activated with different agonists produced intracellular ROSs, wh...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-03-1047
更新日期：2005-10-15 00:00:00
abstract：:An unmet need in cell engineering is the availability of a single transgene encoded, functionally inert, human polypeptide that can serve multiple purposes, including ex vivo cell selection, in vivo cell tracking, and as a target for in vivo cell ablation. Here we describe a truncated human EGFR polypeptide (huEGFRt) ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2011-02-337360
更新日期：2011-08-04 00:00:00
abstract：:The CD11a/CD18 (leukocyte function-associated antigen 1 [LFA-1]) integrin mediates critical leukocyte adhesive interactions during immune and inflammatory responses. The CD11a promoter directs CD11a/CD18 integrin expression, and its activity in lymphoid cells depends on a functional RUNX1/AML-1-binding site (AML-110) ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2003-02-0618
更新日期：2003-11-01 00:00:00
abstract：:Recent studies of retroviral-mediated gene transfer have shown that retroviral integrations themselves may trigger nonmalignant clonal expansion of hematopoietic stem cells (HSCs) in transplant recipients. These observations suggested that previous conclusions of HSC dynamics based on gamma-retroviral gene marking sho...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-03-142661
更新日期：2008-10-15 00:00:00
abstract：:The effect of granulocyte-macrophage colony stimulatory factors (GM-CSF), acidic isoferritins, and E-type prostaglandins on the detection of the cycle status of human granulocyte-macrophage progenitor cells (CFU-GM) was investigated. Bone marrow cells were pulse-treated with control medium or high specific activity tr...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1982-10-01 00:00:00
abstract：:For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2004-03-1193
更新日期：2004-11-01 00:00:00
abstract：:The cyclin-dependent kinase inhibitor p21WAF1/Cip1 and Survivin enhance granulocyte macrophage colony-forming unit (CFU-GM) cell cycle and proliferation and have been implicated as antiapoptotic proteins. We investigated the relationships between p21 and Survivin in primary CFU-GM and c-kit+, lineage-negative (Lin-) c...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2003-05-1756
更新日期：2004-01-01 00:00:00
abstract：:Follicular dendritic cells (FDCs) in the lymphoid follicle (LF) are essential to the sequential processes of B-cell proliferation, selection, and differentiation. Although the importance of some cytokines in these processes has been pointed out, there is little information about the follicular localization of their re...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1997-12-15 00:00:00
abstract：:Lymphomatoid granulomatosis (LyG) is an angiodestructive lymphoproliferative disorder (LPD) often involving the lungs. Its etiology is uncertain, but a number of previous studies had suggested it is a T-cell LPD associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymp...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Maintaining a steady pool of self-renewing hematopoietic stem cells (HSCs) is critical for sustained production of multiple blood lineages. Many transcription factors and molecules involved in chromatin and epigenetic modifications have been found to be critical for HSC self-renewal and differentiation; however, their...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2010-09-306563
更新日期：2011-02-17 00:00:00
abstract：:Escape from immune detection favors both tumor survival and progression, and new approaches to circumvent this are essential to combat cancers. Nonvirulent, tumor-tropic bacteria, such as Salmonella typhimurium, can unmask a tumor by transforming it into a site of inflammation; however, the nonspecific invasiveness of...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2012-12-474098
更新日期：2013-08-01 00:00:00
abstract：:The bcr-abl translocation characteristic of chronic myeloid leukemia (CML) was detected by the polymerase chain reaction (PCR) modified to use mRNA as the starting material. Amplification of a sequence spanning the bcr-abl junction was obtained by using peripheral blood cells from all of 20 patients with classic CML, ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Oxidative stress has been implicated in the triggering of apoptosis in neutrophils. Because red blood cells (RBCs) are well known to scavenge oxidants including H2O2, we tested the hypothesis that RBCs inhibit apoptosis of neutrophils by reducing intracellular oxidative stress. Apoptosis of neutrophils was evaluated b...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1999-06-01 00:00:00
abstract：:Reactivation of fetal hemoglobin remains a critical goal in the treatment of patients with sickle cell disease and β-thalassemia. Previously, we discovered that silencing of the fetal γ-globin gene requires the erythroid-specific eIF2α kinase heme-regulated inhibitor (HRI), suggesting that HRI might present a pharmaco...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.2020005301
更新日期：2020-06-11 00:00:00
abstract：:Ionophore A23187-induced 14C-serotonin secretion and thromboxane B2(TxB2) formation were found to be absent in citrated platelet-rich plasma (PRP) from thrombasthenic subjects and in normal PRP treated with glycoprotein (GP) IIb-IIIa complex-specific monoclonal antibodies. Both responses were restored to normal levels...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanic...
journal_title：Blood
pub_type： 杂志文章,多中心研究
doi：10.1182/blood-2009-03-209221
更新日期：2009-10-08 00:00:00
abstract：:We found an unusual fc gamma receptor IIIa (CD16) phenotype on the natural killer (NK) cells of a 3-year-old boy, who suffered from recurrent viral respiratory tract infections since birth. He also had severe clinical problems after Bacille Calmette-Geérin (BCG) vaccination and following Epstein-Barr virus and Varicel...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1996-10-15 00:00:00
abstract：:We investigated the correlation between the detection of clonal rearrangement of the T-cell antigen receptor gene (TCRR) in lymph node tissue with histopathologic lymph node classification in 33 patients with mycosis fungoides with and without the Sezary Syndrome. We analyzed DNA extracted from lymph nodes that were h...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-06-15 00:00:00
abstract：:Tumors have several mechanisms to escape from the immune system. One of these involves expression of intracellular anticytotoxic proteins that modulate the execution of cell death. Previously, we have shown that the serine protease inhibitor (serpin) SPI-6, which inactivates the cytotoxic protease granzyme B (GrB), is...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2004-03-0791
更新日期：2005-02-01 00:00:00
abstract：:Allelic loss at nonrandom chromosomal sites is thought to mark the position of tumor suppressor genes involved in the pathogenesis and progression of human malignancies. Solid tumors in particular have been found to harbor multiple genetic changes resulting in loss of function mutations. Tumor suppressor genes have al...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1996-10-15 00:00:00
abstract：:We have used monoclonal antibodies (M Abs) and proteolytic fragmentation to localize structurally the functional sites of human von Willebrand factor (vWF) responsible for interaction with membrane glycoproteins GPIb, GPIIb/IIIa, and with collagen. SpII (215 kd) and SpIII (320 kd), the S aureus V-8 protease homodimeri...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1986-05-01 00:00:00
abstract：:Mycobacterium avium-intracellulare (MAI) is an opportunistic pathogen commonly found in acquired immunodeficiency syndrome patients, whose immune systems are severely compromised. However, normal responses to this bacterium are apparently sufficient to prevent disseminated infection because disease is rarely found unl...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1991-05-15 00:00:00
abstract：:Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induce...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1999-03-01 00:00:00
abstract：:Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter doubl...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.2019004596
更新日期：2020-07-09 00:00:00
abstract：:Dysregulation of polycomb repressive complex 2 (PRC2) promotes oncogenesis partly through its enzymatic function for inducing trimethylation of histone H3 lysine 27 (H3K27me3). However, it remains to be determined how PRC2 activity is regulated in normal and diseased settings. We here report a PRC2-associated cofactor...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.2019000578
更新日期：2019-10-03 00:00:00
abstract：:The relationship between platelet density and platelet age appears to vary between species with relatively few labeling studies in humans reported. In this study, irreversible monoamine oxidase (MAO) inhibitors were used to biochemically label the circulating platelet population in 15 humans. Platelet samples were the...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Interleukin 21 (IL-21) is a member of the common gamma-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we ge...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-05-021600
更新日期：2007-03-01 00:00:00
abstract：:To directly determine whether the mechanism of activation of human plasminogen (HPg) by staphylokinase (Sak) required formation of an active complex of Sak and HPg, recombinant (r) variants of HPg were examined that allowed dissection of the steps involved in this activation. The rate of activation of wild-type (wt) r...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:The blood platelet is the only human cell known to have a circumferential band of microtubules. However, the mechanisms involved in assembly of the multi-looped coil, its interaction with the cell membrane to support discoid shape, and constriction into tight rings around centrally concentrated organelles in activated...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
