Abstract：
:Transforming growth factor β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFβ response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFβ signaling effector molecule p57 was found to be upregulated as a secondary response to TGFβ. We observed Gata2 binding upstream of the p57 genomic locus, and importantly, loss of Gata2 abolished TGFβ-stimulated induction of p57 as well as the resulting growth arrest of hematopoietic progenitors. Our results connect key molecules involved in hematopoietic stem cell self-renewal and reveal a functionally relevant network, regulating proliferation of primitive hematopoietic cells.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Billing M,Rörby E,May G,Tipping AJ,Soneji S,Brown J,Salminen M,Karlsson G,Enver T,Karlsson Sdoi
10.1016/j.exphem.2016.02.001subject
Has Abstractpub_date
2016-05-01 00:00:00pages
399-409.e5issue
5eissn
0301-472Xissn
1873-2399pii
S0301-472X(16)00040-0journal_volume
44pub_type
杂志文章abstract：:It is known that inadequate erythropoietin (EPO) production contributes to the pathogenesis of anemia of inflammation, although the exact molecular mechanism is unknown. Aryl hydrocarbon receptor (AhR) may compete with hypoxia-inducible factor 2α (HIF-2α), the master regulator of EPO production, for binding with HIF-1...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.08.010
更新日期：2016-01-01 00:00:00
abstract：:During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:Bone marrow cell responses to therapeutic doses of cis-diamminedichloroplatinum (II) (Cis-Pt) were evaluated in female C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFUS) after treatment. Although limitation on the dosage of Cis-Pt is generally considered to be...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, C...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-04-01 00:00:00
abstract：:Cells of the murine interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) factor-dependent line, FDC-P1, express the tyrosine kinase receptor, c-kit. The ligand for c-kit, steel factor (SLF), encoded by the steel (Sl) locus, is produced as both membrane-bound and soluble forms by fibroblast...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:The results and complications of 224 marrow collections from 200 patients with malignant disease who underwent marrow aspiration and storage for subsequent autologous marrow transplantation (AMT) were analyzed. The median age of the patients was 35 years (range 1-68); 131 patients had hematologic malignancies and 69 h...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal me...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2016.12.007
更新日期：2017-04-01 00:00:00
abstract：:Growth and differentiation of hematopoietic stem cells occur in close contact with the cells and extracellular-matrix (ECM) proteins of the hematopoietic microenvironment. We observed the role of fibronectin, a matrix glycoprotein proposed to be involved in the attachment of hematopoietic cells and in the binding of s...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Coculture of cytotoxic T cells (STIL-3 C5) derived from L8313 leukemic mice with hematopoietic supportive stromal cells (MS-5) resulted in the detachment of MS-5 cells from the culture dish, whereas helper T cells (STIL-3 DF) did not induce this detachment. The response of bone marrow (BM) adherent cells to the same t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：OBJECTIVE:To examine the possibility of adoptive cellular immunotherapy such as donor lymphocyte infusion using ex vivo expanded cord blood (CBL) lymphocytes, the potential expansion ability of CBL lymphocytes and the function of expanded CBL lymphocytes were evaluated. MATERIALS AND METHODS:Mononuclear cell fractions...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00776-2
更新日期：2002-04-01 00:00:00
abstract：:Myelodysplastic syndrome is a clonal process characterized by ineffective hematopoiesis and progression to acute leukemia. Although many myelodysplastic syndrome and leukemic patients have compromised immunity, the role of underlying mutations in regulating immune function is poorly understood. Recent studies show tha...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.05.002
更新日期：2012-08-01 00:00:00
abstract：:The presence of multilineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in the World Health Organization classification with still-debated prognostic value. A major controversy concerns MLD's role in NPM1-mutated (NPM1⁺) AML, which correlates with good prognosi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.06.003
更新日期：2015-10-01 00:00:00
abstract：OBJECTIVE:Many clinical gene therapy trials have described poor engraftment of retrovirally transduced CD34(+) cells. Because engraftment is dependent upon successful homing of graft cells to the bone marrow (BM), we examined whether retroviral-mediated gene transfer (RMGT) induces a homing defect in CD34(+) cells. ME...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.12.014
更新日期：2006-04-01 00:00:00
abstract：:Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express vascular endothelial growth factor (VEGF) as well as Flt-1 and KDR, resulting in an autocrine pathway for cell survival. PTK787/ZK 222584 is a new oral antiangiogenic molecule that inhibits tyrosine kinase ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.03.001
更新日期：2009-06-01 00:00:00
abstract：OBJECTIVE:Donor lymphocyte transfusions (DLT) are effective in the treatment of leukemia after allogeneic stem cell transplantation. Graft-vs-host-disease (GVHD) is the major risk factor of DLT. In dog leukocyte antigen (DLA)-identical littermate dogs, DLT given within 3 weeks after transplantation of marrow depleted o...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.05.001
更新日期：2009-08-01 00:00:00
abstract：:Effects of thyroid hormones on the production of erythropoietin (Epo) were investigated in isolated perfused rat kidneys and in the human hepatoma cell line, HepG2. Epo protein was measured by radioimmunoassay. L-triiodothyronine and L-thyroxine stimulated hypoxia-induced Epo formation both in the kidney and in HepG2 ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-03-01 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：:In hematopoietic cell development, the transcriptional program is strictly regulated in a lineage- and stage-specific manner that requires a number of transcription factors to work in a cascade or in a loop, in addition to interactions with nonhematopoietic cells in the microenvironment. Disruption of the transcriptio...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.06.001
更新日期：2017-09-01 00:00:00
abstract：:Mouse hematopoietic stem cells (HSCs) are highly enriched in the rare (approximately 0.05%) Thy-1.1(lo)Lin(-/lo)Sca-1+ fraction of hematopoietic tissues. It has been demonstrated that Thy-1.1(lo)Lin(-/lo)Sca-1+ cells are the only HSCs in C57BL/Ka-Thy-1.1 bone marrow. In this study, we separated C57/Ka-Thy-1.1 bone mar...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：OBJECTIVE:Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.07.004
更新日期：2010-11-01 00:00:00
abstract：OBJECTIVE:To identify genes involved in megakaryopoiesis, high-density oligonucleotide microarrays were used to compare transcript profiles from undifferentiated CD34+CD38lo cells and culture-derived megakaryocytes (MKs). MATERIALS AND METHODS:Megakaryocyte differentiation was achieved in vitro by inducing primary hum...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.04.002
更新日期：2004-07-01 00:00:00
abstract：:Lifelong blood production is ensured by a population of rare and largely quiescent, long-lived hematopoietic stem cells (HSCs). The advent of single-cell technologies has recently highlighted underlying molecular and functional heterogeneity within the HSC pool. Despite heterogenous HSC behaviors, quiescence remains a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.11.003
更新日期：2020-12-01 00:00:00
abstract：:Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. Microtubule-organizing centers (MTOCs) mediate organization of the mitotic spindle apparatus that separates the chromosomes during mitosis and are known to be crucial for proper cytokinesis. However, the role of MTOCs i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.12.003
更新日期：2016-04-01 00:00:00
abstract：OBJECTIVE:Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycoph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00868-8
更新日期：2002-09-01 00:00:00
abstract：:The effect of staurosporine, a novel calcium/phospholipid-dependent protein kinase (protein kinase C) inhibitor, on differentiation of human promyelocytic leukemic HL-60 cells, was investigated. Staurosporine inhibited HL-60-cell proliferation in a concentration-dependent manner, but did not induce HL-60-cell differen...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:Malignant osteopetrosis is a disorder characterized by a deficiency in osteoclast number or function. In one animal model of osteopetrosis, the op/op mouse, macrophage colony-stimulating factor (M-CSF) is absent, and the administration of M-CSF corrects the defects. We evaluated the serum of 13 patients with malignant...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS:Marrow of 5-fluorouracil pretreated donor mice were transfected wit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00487-2
更新日期：2000-08-01 00:00:00
abstract：OBJECTIVE:The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. MATERIALS AND METHODS...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2003.08.016
更新日期：2003-12-01 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：:[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
