Abstract:
:The transcription factor SCL is critically required for establishing hematopoiesis and for proper endothelial development, but not for maintenance of hematopoietic stem cells or endothelial cells in the adult. Conflicting data exists regarding the developmental function of SCL, namely, whether it acts as a master regulator, actively patterning mesoderm toward hematopoietic development at the expense of other lineages, or is merely necessary to maintain the earliest committed hematopoietic precursors. To answer this question, we have engineered murine embryonic stem cells with a conditional doxycycline-inducible SCL transgene, and evaluated the effects of SCL expression at defined time points during in vitro development. Continual SCL expression during differentiation results in markedly increased hematopoiesis. By using pulses of gene expression over a 6-day differentiation time course, we map and characterize windows of SCL responsiveness. Notably, a pulse of SCL expression during early mesodermal patterning (48 to 72 hours of differentiation) promoted Flk1+ PDGFRalphaneg presumptive extraembryonic/lateral plate mesoderm at the expense of PDGFRalpha+ Flk1neg presumptive paraxial mesoderm. Consistent with this, the early pulse of SCL expression also expanded hematopoietic colony-forming cell numbers, while concomitantly repressing expression of paraxial and cardiac markers, and inhibited development of beating cardiomyocytes. By mixing the inducible embryonic stem cells with fluorescently labeled wild-type cells in chimeric embryoid bodies, we show that these effects of SCL are cell autonomous. These data support a master-regulatory role for SCL in mesodermal patterning, in addition to its established later roles in hematopoietic differentiation.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Ismailoglu I,Yeamans G,Daley GQ,Perlingeiro RC,Kyba Mdoi
10.1016/j.exphem.2008.07.005subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1593-603issue
12eissn
0301-472Xissn
1873-2399pii
S0301-472X(08)00351-2journal_volume
36pub_type
杂志文章abstract:OBJECTIVE:Assays that can evaluate the potential of individual human hematopoietic stem cells (HSC) are still lacking. We previously developed the myeloid-lymphoid initiating cell (ML-IC) assay that enumerates single CD34(+) cells that generate long-term culture-initiating (LTC-IC) and NK-initiating (NK-IC) daughter ce...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.10.016
更新日期:2005-02-01 00:00:00
abstract::C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PE...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult A...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.02.010
更新日期:2016-06-01 00:00:00
abstract::The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract::Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DN...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity....
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract:OBJECTIVE:To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS:Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00137-5
更新日期:2000-05-01 00:00:00
abstract:OBJECTIVE:Hemopoiesis is regulated by cytokines with positive or negative effects on proliferation of lineage-committed or multipotent hemopoietic stem cells. We have investigated the roles of interleukin-6 and other gp130-dependent ligands on the proliferation of macrophage-lineage hemopoietic progenitor cells. METHO...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00512-9
更新日期:2000-10-01 00:00:00
abstract::Cells for study were obtained from mouse bone marrow by three methods: 1) Mechanical dissociation; 2) Trypsin release; and 3) Passage through a syringe and needle. The ratio of the fibroblast colony-forming cells in these suspensions was, respectively, 1:13:1. Of the colonies formed by cells obtained by trypsin releas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular dNTP homoeostasis. Mutations in SAMHD1 have been associated with the hyperinflammatory disease Ai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.05.001
更新日期:2017-08-01 00:00:00
abstract:OBJECTIVE:Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained rem...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.022
更新日期:2006-09-01 00:00:00
abstract::Autotaxin (ATX) has been reported to act as a motility and growth factor in a variety of cancer cells. The ATX protein acts as a secreted lysophospholipase D by converting lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which signals via G-protein-coupled receptors and has important functions in cell mig...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.01.007
更新日期:2013-05-01 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:OBJECTIVE:Polycythemia rubra vera-1 (PRV-1) is a GPI-linked protein that is expressed on a subgroup of neutrophils. The number of PRV-1-expressing neutrophils increases in pregnancy and sepsis, or after administration of granulocyte colony-stimulating factor. Expression of the PRV-1 gene is also increased in patients w...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.09.008
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:The mechanism for anagrelide's potent platelet lowering activity in human subjects is not well defined. Studies related to anagrelide function have been hampered by its lack of activity in nonhuman primates and water insolubility. In an effort to define the mechanism whereby anagrelide exerts its therapeutic ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00742-1
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:Several requirements need to be fulfilled for clinical use of expanded hematopoietic stem cells (HSCs). Because most cord blood (CB) samples are frozen in single bags and only an aliquot ( approximately 25%) of the blood can be expanded, the thawing and refreezing of samples must be validated in the current E...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.exphem.2007.08.030
更新日期:2008-02-01 00:00:00
abstract::The effect of recombinant interleukin 3 (IL-3) on the function of murine resident peritoneal macrophages was investigated. IL-3 enhanced the phagocytosis of Candida pseudotropicalis and Candida albicans and enhanced killing of the former. The enhanced killing is inhibited by scavengers of oxygen radicals, suggesting t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Collagen gel was used as a substance for the assay of human granulocyte-macrophage colony-forming units (CFUc). The number of colonies formed in collagen gel was consistently higher than that in a conventional soft-agar system. In six out of eight experiments, the difference was statistically significant. Whole perman...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract:OBJECTIVE:Hematopoietic stem and progenitor cells normally reside in the bone marrow but can be mobilized into the peripheral blood following treatment with granulocyte colony-stimulating factor (G-CSF) or myelosuppressive chemotherapy. Although the number of transplants performed with mobilized blood currently exceeds...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00788-9
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVE:To examine whether oncogenic Ras affects transforming growth factor (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream signal transduction pathway involved in the interference with TGF-beta-induced cell-cycle arrest. MATERIALS AND METHODS:Two leukemic cell lines bearing N-Ras(L61...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.04.006
更新日期:2005-07-01 00:00:00
abstract:OBJECTIVE:To investigate 1) the signal transduction pathways affected by heat shock protein 27 (HSP27) expression; and 2) the expression and regulation of HSP27 in acute myeloid leukemia (AML). MATERIALS AND METHODS:RNA interference studies for HSP27 in leukemic TF-1 cells were used to investigate the effects on downs...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.03.009
更新日期:2005-06-01 00:00:00
abstract::A most stringent test for the non-identity of biologically active materials is provided by the techniques used for parallel line type bioassay of these materials. We have studied commercially available GCT conditioned medium using a parallel line type biological assay for granulocyte-macrophage colony stimulating fact...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::Cyclooxygenase (COX) plays a key regulatory role in prostaglandin synthesis. COX-2 is inducible and is the major isoform of inflammatory cells. COX-2-deficient mice were shown to have normal basal hematopoiesis and hematology. We hypothesized that COX-2 induction plays a role in the recovery phase of 5-fluorouracil (5...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00087-9
更新日期:1999-10-01 00:00:00
abstract::Discontinuous albumin density gradients were used to physically separate hemopoietic cells from immunocompetent lymphocytes in peripheral blood mononuclear cells of dogs. Transplantation of these stem cell concentrates into lethally irradiated allogeneic recipients restored hemopoiesis in nine of 12 animals. Tolerance...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Clonality studies can establish the single-cell origin of tumors and thus differentiate clonal malignant and premalignant processes from reactive polyclonal processes. Detection of clonal cells may be based on direct tracking of cell lineage-specific sequences or disease-specific somatic mutations identifying the clon...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.01.013
更新日期:2020-03-01 00:00:00
abstract::Murine low-density bone marrow cells sorted from the blast cell window on the basis of high rhodamine-123 retention (Rh-bright), are highly enriched in histamine-, IL-4-, and IL-6-producing cells. We established by in situ hybridization that up to 50% of this population (around 0.25% of the whole bone marrow) coexpres...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00039-9
更新日期:1999-06-01 00:00:00
abstract::With a new labeling technique in radiation chimeras, an attempt was made to determine the duration of the phases of the stem cell cycle including shortest and mean generation time and to estimate the number of hemopoietic stem cells per unit of bone marrow cellularity. The DNA of bone marrow cells in DNA synthesis was...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-10-01 00:00:00
abstract:OBJECTIVE:To investigate the interaction of imatinib mesylate (IM) with the clinically relevant adenosine triphosphate-binding cassette efflux transporter MDR1 (ABCB1) in cells from patients with chronic myeloid leukemia (CML) and to explore whether inhibition of this transporter would improve IM's efficacy in the elim...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.02.006
更新日期:2009-06-01 00:00:00