Abstract：
:Haploinsufficiency of erythroid Krüppel-like factor (EKLF/KLF1) has been shown recently to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. In this study, we used a combination of in silico, in vitro, and in vivo approaches to identify microRNAs (miRs) involved in EKLF regulation and to validate the role of miR-326 in HbF modification. We found that miR-326 suppresses EKLF expression directly by targeting its 3' untranslated region. miR-326 overexpression in K562 cells or CD34+ hematopoietic progenitor cells resulted in reduced EKLF protein levels and was associated with elevated expression of γ-globin, whereas inhibition of physiological miR-326 levels increased EKLF and thus reduced γ-globin expression. Moreover, miR-326 expression is positively correlated with HbF levels in β-thalassemia patients. Our results suggest that miR-326 plays a key role in regulating EKLF expression and in modifying the HbF level, which may provide a new strategy for activating HbF in individuals with β-thalassemia or sickle cell disease.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Li Y,Liu D,Zhang X,Li Z,Ye Y,Liu Q,Shen J,Chen Z,Huang H,Liang Y,Han X,Liu J,An X,Mohandas N,Xu Xdoi
10.1016/j.exphem.2018.03.004subject
Has Abstractpub_date
2018-07-01 00:00:00pages
33-40.e2eissn
0301-472Xissn
1873-2399pii
S0301-472X(18)30162-0journal_volume
63pub_type
杂志文章abstract：OBJECTIVE:The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environm...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.11.011
更新日期：2005-03-01 00:00:00
abstract：:Using an accurate technique for staining and scoring soft agar cultures, this study defines the incidence of circulating CFUEOS in normal donors. With whole mononuclear cells as the source of colony stimulating factor (CSF) and fetal calf serum, 49.6% +/- 3.5 of the colonies were eosinophilic; with human placental con...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:The synthesis and expression of protein complexes of 23,000 and 30,00 dalton (p23,30) HLA-DR antigen, and of 44,000 and 12,000 dalton (p44,12) HLA-A,B antigen and beta 2-microglobulin was demonstrated on human peripheral blood monocytes and in cultures of purified, adherent monocytes. In indirect immunofluorescence as...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:Peripheral blood and bone marrow specimens from patients with polycythemia vera (PV) and chronic myelogenous leukemia (CML) were assayed for erythroid and granulopoietic progenitor cells. All compartments were increased in CML patients in relapse although the ratio of BFU-E to CFU-C numbers remained constant in all CM...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:The proliferative capacity of partially purified populations of mouse bone marrow progenitor cells has been examined in serum-free cultures in the presence and absence of colony-stimulating factors (CSFs). The half-life of progenitor cells was approximately 25 h in the absence of factor, regardless of whether the fact...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated splee...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:The selection of chemotherapy regimen for elderly patients with acute myeloid leukemia (AML) remains challenging. Here, we report that granulocyte colony-stimulating factor (G-CSF) upregulates the expression of microRNA (miR)-146a in a nuclear factor kappaB-dependent manner, leading to direct decreases in the expressi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.09.002
更新日期：2018-12-01 00:00:00
abstract：OBJECTIVE:It has been shown previously that infection with diverse viruses induces alterations in bone marrow lineage-specific progenitor cells. As complications arising from secondary bacterial infections can adversely affect the host, we investigated whether virally induced hematological alterations could contribute ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.09.005
更新日期：2005-12-01 00:00:00
abstract：:In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:The transcription factor RUNX1 is required in the embryo for formation of the adult hematopoietic system. Here, we describe the seminal findings that led to the discovery of RUNX1 and of its critical role in blood cell formation in the embryo from hemogenic endothelium (HE). We also present RNA-sequencing data demonst...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2018.10.009
更新日期：2018-12-01 00:00:00
abstract：OBJECTIVE:We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning. METHODS:Nonmyeloablative conditioning consisted of 2 Gy total-body irradiation+/-flud...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(03)00201-7
更新日期：2003-10-01 00:00:00
abstract：OBJECTIVE:Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of by...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.01.014
更新日期：2007-04-01 00:00:00
abstract：:Despite its growing use as a marker of proliferation, the relationship between expression of the nuclear antigen Ki67 and other indices of proliferation in acute myelogenous leukemia (AML) has not been elucidated. In this study, short-term primary suspension cultures of human AML bone marrow cells were used to compare...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:Committed erythroid progenitor cells (Colony Forming Units-Erythroid, CFU-E) have been studied in canine cyclic hematopoiesis (CH) utilizing a semi-solid methyl cellulose culture system. Erythroid colonies were stimulated by the addition of a standard volume of serum from normal dogs that had been phlebotomized and su...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-10-01 00:00:00
abstract：OBJECTIVE:The OP9-DL1 culture system is an in vitro model for T-cell development in which activation of the Notch pathway by Delta-like 1 promotes differentiation of mature T cells from progenitors. The roles of specific cytokines in this culture system have not been well defined, and controversy regarding the role of ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.08.001
更新日期：2006-12-01 00:00:00
abstract：:A fluorescence-activated cell sorter has been used to sort out enriched populations of murine hemopoietic stem cells from mouse bone marrow, based on fluorescence of cells labeled with various antisera. Significant positive enrichment for stem cells was obtained with rabbit anti-human brain, human anti-human sperm and...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：:Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compar...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：:In a previous report, we described a method to generate cell lines derived from stromal colonies (colony-derived cell lines [CDCL]). In a first step, colonies were obtained from plating cells from adherent layers of human long-term bone marrow cultures (LTBMC) in methyl-cellulose in the presence of interleukin-1 beta ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:The objectives of this review were first to critically review what is known about the effects of aging on stem cells in general, and hematopoietic stem cells in particular. Secondly, evidence is marshalled in support of the hypothesis that aging stem cells play a critical role in determining the effects of aging on or...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/s0301-472x(03)00088-2
更新日期：2003-08-01 00:00:00
abstract：:In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Studies were undertaken to produce monoclonal antibodies directed against the murine receptor for macrophage colony-stimulating factor (M-CSF or CSF-1). Sprague-Dawley rats were injected with lysates prepared from a murine myelomonocytic cell line (RAW cell line) that has high levels of M-CSF receptors. Spleen cells f...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.03.002
更新日期：2010-06-01 00:00:00
abstract：:BCR-ABL-negative myeloproliferative neoplasms (MPNs) are driven by JAK-STAT pathway activation, but epigenetic alterations also play an important pathophysiological role. These can be pharmacologically manipulated with histone deacetylase inhibitors (HDACIs), which have proven to be clinically effective in the treatme...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.02.002
更新日期：2019-04-01 00:00:00
abstract：OBJECTIVE:For approximately 5% of autologous transplant recipients and a higher proportion of allogeneic transplant recipients, low level and delayed platelet engraftment is an ongoing problem. Mesenchymal stem cells (MSC), which can be derived from bone marrow as well as other organs, are capable of differentiation in...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(03)00042-0
更新日期：2003-05-01 00:00:00
abstract：:Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. MATERIALS AND METHODS:We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSC)-containin...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00835-4
更新日期：2002-07-01 00:00:00
abstract：:Conditions that allow the growth of canine marrow cells in long-term marrow culture are described. The quality of the culture conditions was evaluated based on the weekly number of granulocyte-macrophage colony-forming units (CFU-GM) in the nonadherent cell fraction. Using this parameter, the highest number of CFU-GM ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:Exit of primitive hematopoietic progenitor cells (HPCs) from the G0 phase of the cell cycle in response to in vitro cytokine stimulation is a limiting step in successful ex vivo expansion. Simultaneous DNA/RNA staining with Hoechst 33342 and pyronin Y was used to separate human bone marrow CD34+ cells residing in G0 (...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells. Although many of these transcription factors have putative roles based on murine knockout experiments, their function in human lymphoid development is less known and was studied further. ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00680-9
更新日期：2001-04-01 00:00:00
