Abstract：
:Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found insulin-like growth factor 2 (IGF2) to be expressed predominantly within long-term HSCs. This study examines IGF2 expression patterns and the effects of the gene in HSCs. Through the overexpression and knockdown of IGF2 within purified HSCs, we report that IGF2 expression increases HSC-derived multilineage colonies in vitro and enhances hematopoietic contribution in vivo on competitive bone marrow transplantation. The effects of IGF2 are mediated by direct upregulation of the CDKi p57, exclusively within long-term HSCs, via activation of the PI3K-Akt pathway. Increased expression of p57 resulted in a concomitant increase in HSCs in the G0/G1 stage of the cell cycle. Analysis of genomic DNA methylation revealed that HSCs exhibited a hypomethylated state within the promoter region of the CDKN1C (p57) gene, providing a potential mechanism for the exclusive effects of IGF2 within HSCs. Our studies indicate a novel role for IGF2 in regulating HSC cell cycle and illustrate potential novel therapeutic targets for hematologic diseases.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Thomas DD,Sommer AG,Balazs AB,Beerman I,Murphy GJ,Rossi D,Mostoslavsky Gdoi
10.1016/j.exphem.2016.01.010subject
Has Abstractpub_date
2016-05-01 00:00:00pages
422-433.e1issue
5eissn
0301-472Xissn
1873-2399pii
S0301-472X(16)00039-4journal_volume
44pub_type
杂志文章abstract：:Normal and myeloid leukemic spleen cells from RF mice were cultured in vitro in plasma clots. In situ histochemical staining and karyotypic analysis of the colonies formed in the clot revealed that the colonies produced by leukemic and normal progenitors were indistinguishable morphologically and cytochemically. Colon...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:Heterozygous alpha-thalassemic (Hbath/+) female mice were investigated for the effect of persistent erythropoietic stress on the number of stem cells and progenitor cells along the the erythroid (E), granulocyte-macrophage (GM), and megakaryocyte (Meg) pathways. At the progenitor cell level, compensatory erythropoiesi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-05-01 00:00:00
abstract：:Initially described as an endogenous inhibitor of proteases, the tissue inhibitor of metalloproteinases 1 (TIMP-1) also displays cytokine-like functions. TIMP-1 is a soluble protein whose levels are increased under inflammatory conditions. We recently found that TIMP-1(-/-) mice have decreased bone marrow (BM) cellula...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.07.003
更新日期：2015-11-01 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：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：:Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-03-01 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：OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.11.005
更新日期：2007-03-01 00:00:00
abstract：:Normal human peripheral blood mononuclear cells (MNCs), particularly T lymphocytes (T cells), are a rich source of granulocyte-macrophage colony-stimulating factor (GM-CSF). Glucocorticoids are known to inhibit GM-CSF production in in vitro cultures of a human fibroblast cell line and in normal human blood monocytes a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:We present the first report of a T-helper cell line, HUT 102, constitutively producing both granulocyte-macrophage colony-stimulating factor (GM-CSF) and monocytic colony-stimulating factor (M-CSF), as detected by sensitive enzyme-linked immunosorbent assays and Northern blot analysis. However, neither amplification n...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：OBJECTIVE:All-trans retinoic acid (ATRA) has been used as the first-line therapy for patients with acute promyelocytic leukemia (APL). We previously reported that ATRA increased serum thrombopoietin (TPO) levels accompanied by thrombocytosis during ATRA therapy for APL. In this study, we investigated the mechanism of t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2003.10.009
更新日期：2004-01-01 00:00:00
abstract：:We have examined the capacity of highly purified human CD34+ marrow cell isolates from unrelated, HLA-mismatched donors to establish in vitro hematopoiesis on recipient marrow stromal cells in 2-stage hematopoietic long-term marrow cultures (H-LTMC). HLA-typing of both peripheral blood mononuclear cells and CD34+ marr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：OBJECTIVE:Granulocyte colony-stimulating factor (G-CSF) is used to boost granulocyte counts in immunocompromised patients, but its effects on the immune system may be counterproductive. We tested the hypothesis that G-CSF-mobilized peripheral blood stem cell (PBSC) products are immunologically downregulated based on ge...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.06.001
更新日期：2007-09-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development. MATERIALS AND METHODS:Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00128-9
更新日期：2000-01-01 00:00:00
abstract：:Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential h...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expressi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.08.011
更新日期：2015-12-01 00:00:00
abstract：:The expression of exogenous genes in long-lived primary T cells is potentially beneficial for the treatment of various diseases including cancer, AIDS, genetic defects of the lymphoid compartment, and systemic enzyme deficiencies such as hemophilia. One approach for genetic modification of T cells is to introduce ther...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high con...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：OBJECTIVES:We previously demonstrated that allogeneic bone marrow transplantation (BMT) after low-dose total lymphoid irradiation (200 cGy) and depletion of donor-reactive cells with cyclophosphamide (Cy) converted recipients to graft-vs-host disease (GVHD)-free chimeras tolerant to donor skin grafts. BMT also generate...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)01009-3
更新日期：2003-01-01 00:00:00
abstract：:In adult hematopoiesis, the hematopoietic stem cell (HSC) sits at the top of a hierarchy of hematopoietic progenitors responsible for generating the diverse repertoire of blood and immune cells. During embryonic development, however, the initial waves of hematopoiesis provide the first functioning blood cells of the d...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.12.008
更新日期：2018-04-01 00:00:00
abstract：:The etiology of thrombocytopenia is important in treatment and management of the condition. Most platelet parameters that are routinely analyzed in the diagnostic laboratory have not proven useful in identifying the etiology, while specialized assays suffer from poor standardization and lack of agreement between labor...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/j.exphem.2019.09.001
更新日期：2019-10-01 00:00:00
abstract：:It has been demonstrated that genomic alterations of cells in the hematopoietic microenvironment could induce myelodysplastic syndromes (MDS) with ineffective hematopoiesis and dysmorphic hematopoietic cells, and subsequent transformation to acute myeloid leukemia. This investigation is the first attempt to correlate ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.10.009
更新日期：2013-02-01 00:00:00
abstract：:Several studies suggest that serum factors (thrombopoietins) regulate thrombopoiesis by altering the number, size, ploidy, and maturation rate of megakaryocytes (MK). Various in vivo systems have been used to quantitate these events. In this study, an in vitro system was developed to monitor terminal cytoplasmic matur...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：OBJECTIVE:Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia caused by mutations in ribosomal protein (RP) genes. Our aim is to develop gene therapy for DBA patients with mutations in RPS19. We previously demonstrated that RPS19 gene transfer partially corrects erythroid development in vitro. In this...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.06.012
更新日期：2008-11-01 00:00:00
abstract：OBJECTIVE:Podocalyxin expression on Ter119(+) erythroblasts is induced following administration of erythropoietin (Epo) or phenylhydrazine treatment, but is notably absent on committed erythroid progenitors during homeostatic red cell turnover. Following high-dose Epo administration in vivo, podocalyxin surface express...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.09.006
更新日期：2009-01-01 00:00:00
abstract：:Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initial...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Colony formation by megakaryocyte (MK) progenitors was studied in 36 normal individuals and in 26 patients with primary thrombocythemia (PT) using an improved plasma clot cloning system. MK colonies were identified by immunoperoxidase staining using a monoclonal antibody against human platelet glycoprotein IIb/IIIa co...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：OBJECTIVE:Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. METHODS:We t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.02.007
更新日期：2004-05-01 00:00:00
abstract：:The recent cloning of thrombopoietin (TPO) has allowed us to study its in vivo effects in normal and myelosuppressed mice. Normal Balb/c mice were treated with recombinant human TPO (hTPO) at doses ranging from 1 to 20 kU for 7 days, and complete blood counts (CBCs) and the number of megakaryocytes in the bone marrow ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.07.017
更新日期：2004-11-01 00:00:00
