The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform

Wenqing Zhang - One of the best experts on this subject based on the ideXlab platform.

  • sumo1 activating enzyme subunit 1 is essential for the survival of hematopoietic stem progenitor cells in zebrafish
    Development, 2012
    Co-Authors: Xiuling Li, Jin Xu, Wenqing Zhang
    Abstract:

    SUMMARY In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where Hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tango hkz5 , which shows defects of definitive Hematopoiesis. In tango hkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive Hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tango hkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive Hematopoiesis and that the tango hkz5 mutation produces a truncated Sae1 protein (Sae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal Hematopoiesis in zebrafish.

  • SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish
    Development, 2012
    Co-Authors: Xiuling Li, Jin Xu, Wenqing Zhang
    Abstract:

    SUMMARY In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where Hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tango hkz5 , which shows defects of definitive Hematopoiesis. In tango hkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive Hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tango hkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive Hematopoiesis and that the tango hkz5 mutation produces a truncated Sae1 protein (Sae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal Hematopoiesis in zebrafish.

Xiuling Li - One of the best experts on this subject based on the ideXlab platform.

  • sumo1 activating enzyme subunit 1 is essential for the survival of hematopoietic stem progenitor cells in zebrafish
    Development, 2012
    Co-Authors: Xiuling Li, Jin Xu, Wenqing Zhang
    Abstract:

    SUMMARY In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where Hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tango hkz5 , which shows defects of definitive Hematopoiesis. In tango hkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive Hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tango hkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive Hematopoiesis and that the tango hkz5 mutation produces a truncated Sae1 protein (Sae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal Hematopoiesis in zebrafish.

  • SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish
    Development, 2012
    Co-Authors: Xiuling Li, Jin Xu, Wenqing Zhang
    Abstract:

    SUMMARY In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where Hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tango hkz5 , which shows defects of definitive Hematopoiesis. In tango hkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive Hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tango hkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive Hematopoiesis and that the tango hkz5 mutation produces a truncated Sae1 protein (Sae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal Hematopoiesis in zebrafish.

Jonathan Hoggatt - One of the best experts on this subject based on the ideXlab platform.

  • pleiotropic effects of prostaglandin e2 in Hematopoiesis prostaglandin e2 and other eicosanoids regulate hematopoietic stem and progenitor cell function
    Prostaglandins & Other Lipid Mediators, 2011
    Co-Authors: Louis M Pelus, Jonathan Hoggatt
    Abstract:

    Eicosanoids have been implicated in the physiological regulation of Hematopoiesis with pleiotropic effects on hematopoietic stem cells and various classes of lineage restricted progenitor cells. Herein we review the effects of eicosanoids on Hematopoiesis, focusing on new findings implicating prostaglandin E2 in enhancing hematopoietic stem cell engraftment by enhancing stem cell homing, survival and self-renewal. We also describe a role for cannabinoids in Hematopoiesis. Lastly, we discuss the yin and yang of various eicosanoids in modulating hematopoietic stem and progenitor cell functions and summarize potential strategies to take advantage of these effects for therapeutic benefit for hematopoietic stem cell transplantation.

Lisa Garrett - One of the best experts on this subject based on the ideXlab platform.

  • the c terminal of myh11 is required for cbfb myh11 activity during embryonic Hematopoiesis and leukemogenesis
    Blood, 2011
    Co-Authors: Katherine R Hyde, Yasuhiko Kamikubo, Lemlem Alemu, Ling Zhao, Lisa Garrett
    Abstract:

    Abstract 2472 RKH, YK, and LZ all contributed equally to this work Inv(16) is found in nearly all patients with acute myeloid leukemia (AML) subtype M4Eo. Inv(16) results in the fusion of the transcription factor gene CBFB , and the MYH11 gene, which encodes Smooth Muscle Myosin Heavy Chain (SMMHC). This results in the fusion gene CBFB-MYH11 , which encodes CBFβ-SMMHC. Previously we showed that knock-in mice with a single allele of Cbfb-MYH11 ( Cbfb +/MYH11 ) have severe differentiation defects in primitive Hematopoiesis and a total block in definitive Hematopoiesis. In addition, chimeric mice generated from Cbfb +/MYH11 ES cells consistently developed leukemia within a few months after treatment with the mutagen N-ethyl-N-nitrosourea (ENU). It is currently not clear which functional domains of CBFβ-SMMHC are responsible for its activity in differentiation and leukemogenesis. In vitro experiments have indicated that CBFβ-SMMHC can form multimeric complexes via the C terminal domain. It has been postulated that this multimerization may be important for the function of CBFβ-SMMHC by resulting in large macromolecular complexes and/or sequestration of its binding partner, the transcription factor RUNX1. To determine the importance of this domain in vivo, we generated knock-in mice expressing a mutant Cbfb-MYH11 allele with a deletion of the 95 C-terminal amino acids ( Cbfb +/MYH11ΔC95 ). In analysis of primitive Hematopoiesis, we found that Cbfb +/MYH11ΔC95 and Cbfb MYH11ΔC95/MYH11ΔC95 mice had no or very mild differentiation defects, statistically significantly less severe (p Cbfb-MYH11 . During definitive hematopoesis, there were no observable defects in Cbfb +/MYH11ΔC95 mice, but Cbfb MYH11ΔC95/MYH11ΔC95 embryos showed a complete block in definitive Hematopoiesis, as seen in mice expressing a single allele of full length Cbfb-MYH11 . This indicates that Cbfb-MYH11ΔC95 is less effective in blocking differentiation than the full length fusion gene. Interestingly, both the primitive and definitive embryonic blood phenotypes of the Cbfb MYH11ΔC95/MYH11ΔC95 were similar to that observed in embryos lacking functional Cbfb ( Cbfb −/− ), implying that Cbfb-MYH11ΔC95 may act as a null allele. To test this possibility we used gene expression microarrays to compare gene expression profiles in the peripheral blood from embryonic day 12 Cbfb MYH11ΔC95/MYH11ΔC95 , Cbfb −/− , and Cbfb +/MYH11 , as well as their Cbfb +/+ littermates. Surprisingly, Cbfb MYH11ΔC95/MYH11ΔC95 embryos showed deregulated expression of a distinct gene set as compared to both Cbfb −/− and Cbfb +/MYH11 embryos. This implies that Cbfb-MYH11ΔC95 is not a null allele of Cbfb , and likely retains some, but not all, of the neomorph properties of full length Cbfb-MYH11 . Consistent with this finding, we observe the accumulation of abnormal myeloid cells in some adult Cbfb +/MYH11ΔC95 mice after ENU treatment, which has not been reported in Cbfb +/− mice. However, we found that Cbfb-MYH11ΔC95 has not retained the most critical of the fusion gene9s activities: the ability to induce leukemogenesis. Importantly, none of the Cbfb +/MYH11ΔC95 mice developed leukemia after treatment with ENU. This is in contrast to mice expressing full length Cbfb-MYH11 , which all develop leukemia under these conditions. Together, these results indicate that the 95 C-terminal amino acids of CBFβ-SMMHC are required for both embryonic hematopoietic defects and leukemogenesis. Disclosures: No relevant conflicts of interest to declare.

Jin Xu - One of the best experts on this subject based on the ideXlab platform.

  • sumo1 activating enzyme subunit 1 is essential for the survival of hematopoietic stem progenitor cells in zebrafish
    Development, 2012
    Co-Authors: Xiuling Li, Jin Xu, Wenqing Zhang
    Abstract:

    SUMMARY In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where Hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tango hkz5 , which shows defects of definitive Hematopoiesis. In tango hkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive Hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tango hkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive Hematopoiesis and that the tango hkz5 mutation produces a truncated Sae1 protein (Sae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal Hematopoiesis in zebrafish.

  • SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish
    Development, 2012
    Co-Authors: Xiuling Li, Jin Xu, Wenqing Zhang
    Abstract:

    SUMMARY In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where Hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tango hkz5 , which shows defects of definitive Hematopoiesis. In tango hkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive Hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tango hkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive Hematopoiesis and that the tango hkz5 mutation produces a truncated Sae1 protein (Sae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal Hematopoiesis in zebrafish.