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  1. Article ; Online: iPSC diversity: A key for better use and improved targeting.

    Abbonante, Vittorio / Di Buduo, Christian A / Balduini, Alessandra

    Journal of thrombosis and haemostasis : JTH

    2021  Volume 19, Issue 7, Page(s) 1641–1643

    MeSH term(s) Cell Differentiation ; Hepatocytes ; Humans ; Induced Pluripotent Stem Cells
    Language English
    Publishing date 2021-06-25
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1111/jth.15328
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    Zs.A 5805: Show issues Location:
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  2. Article ; Online: GALE

    Marín-Quílez, Ana / Di Buduo, Christian A / Benito, Rocío / Balduini, Alessandra / Rivera, José / Bastida, Jose Maria

    Platelets

    2023  Volume 34, Issue 1, Page(s) 2176699

    Abstract: ... ...

    Abstract GALE
    MeSH term(s) Humans ; Galactose ; Galactosemias/genetics ; Hemorrhage ; Thrombocytopenia/genetics ; UDPglucose 4-Epimerase/genetics
    Chemical Substances Galactose (X2RN3Q8DNE) ; UDPglucose 4-Epimerase (EC 5.1.3.2)
    Language English
    Publishing date 2023-02-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2023.2176699
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Bone marrow microenvironment of MPN cells.

    Malara, Alessandro / Di Buduo, Christian A / Abbonante, Vittorio / Balduini, Alessandra

    International review of cell and molecular biology

    2021  Volume 365, Page(s) 71–96

    Abstract: In this chapter, we will discuss the current knowledge concerning the alterations of the cellular components in the bone marrow niche in Myeloproliferative Neoplasms (MPNs), highlighting the central role of the megakaryocytes in MPN progression, and the ... ...

    Abstract In this chapter, we will discuss the current knowledge concerning the alterations of the cellular components in the bone marrow niche in Myeloproliferative Neoplasms (MPNs), highlighting the central role of the megakaryocytes in MPN progression, and the extracellular matrix components characterizing the fibrotic bone marrow.
    MeSH term(s) Bone Marrow ; Bone Marrow Cells ; Humans ; Megakaryocytes ; Myeloproliferative Disorders
    Language English
    Publishing date 2021-10-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2021.07.001
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  4. Article ; Online: Sirtuin 6 Regulates the Activation of the ATP/Purinergic Axis in Endothelial Cells.

    Astigiano, Cecilia / Piacente, Francesco / Laugieri, Maria Elena / Benzi, Andrea / Di Buduo, Christian A / Miguel, Carolina P / Soncini, Debora / Cea, Michele / Antonelli, Antonella / Magnani, Mauro / Balduini, Alessandra / De Flora, Antonio / Bruzzone, Santina

    International journal of molecular sciences

    2023  Volume 24, Issue 7

    Abstract: Sirtuin 6 (SIRT6) is a member of the mammalian ... ...

    Abstract Sirtuin 6 (SIRT6) is a member of the mammalian NAD
    MeSH term(s) Humans ; Adenosine Triphosphate ; Human Umbilical Vein Endothelial Cells/metabolism ; NAD ; Sirtuins/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
    Chemical Substances Adenosine Triphosphate (8L70Q75FXE) ; NAD (0U46U6E8UK) ; SIRT6 protein, human (EC 3.5.1.-) ; Sirtuins (EC 3.5.1.-) ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-04-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24076759
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  5. Article ; Online: Newly identified roles for PIEZO1 mechanosensor in controlling normal megakaryocyte development and in primary myelofibrosis.

    Abbonante, Vittorio / Karkempetzaki, Anastasia Iris / Leon, Catherine / Krishnan, Anandi / Huang, Nasi / Di Buduo, Christian A / Cattaneo, Daniele / Ward, Christina Marie / Matsuura, Shinobu / Guinard, Ines / Weber, Josiane / De Acutis, Aurora / Vozzi, Giovanni / Iurlo, Alessandra / Ravid, Katya / Balduini, Alessandra

    American journal of hematology

    2024  Volume 99, Issue 3, Page(s) 336–349

    Abstract: Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation in health and disease are still partially understood. We found PIEZO1, a mechanosensitive cation ... ...

    Abstract Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation in health and disease are still partially understood. We found PIEZO1, a mechanosensitive cation channel, to be expressed in mouse and human Mks. Human mutations in PIEZO1 have been described to be associated with blood cell disorders. Yet, a role for PIEZO1 in megakaryopoiesis and proplatelet formation has never been investigated. Here, we show that activation of PIEZO1 increases the number of immature Mks in mice, while the number of mature Mks and Mk ploidy level are reduced. Piezo1/2 knockout mice show an increase in Mk size and platelet count, both at basal state and upon marrow regeneration. Similarly, in human samples, PIEZO1 is expressed during megakaryopoiesis. Its activation reduces Mk size, ploidy, maturation, and proplatelet extension. Resulting effects of PIEZO1 activation on Mks resemble the profile in Primary Myelofibrosis (PMF). Intriguingly, Mks derived from Jak2
    MeSH term(s) Humans ; Animals ; Mice ; Megakaryocytes/metabolism ; Primary Myelofibrosis/genetics ; Bone Marrow ; Thrombopoiesis/genetics ; Thrombocythemia, Essential/metabolism ; Blood Platelets/metabolism ; Ion Channels/genetics ; Ion Channels/metabolism
    Chemical Substances PIEZO1 protein, human ; Ion Channels ; Piezo1 protein, mouse
    Language English
    Publishing date 2024-01-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.27184
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    Zs.A 1251: Show issues Location:
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  6. Article ; Online: Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells.

    Antonelli, Antonella / Scarpa, Emanuele Salvatore / Bruzzone, Santina / Astigiano, Cecilia / Piacente, Francesco / Bruschi, Michela / Fraternale, Alessandra / Di Buduo, Christian A / Balduini, Alessandra / Magnani, Mauro

    International journal of molecular sciences

    2023  Volume 24, Issue 6

    Abstract: Sinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone ...

    Abstract Sinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone marrow hematopoietic niche, the oxygen tension is usually very low, and this condition affects stem and progenitor cell proliferation and differentiation and other important functions of this region. Here, we have investigated in vitro the response of endothelial cells to a marked decrease in O
    MeSH term(s) Hematopoietic Stem Cells/metabolism ; Endothelial Cells/metabolism ; Cells, Cultured ; Bone Marrow/metabolism ; Interleukins/metabolism ; Sirtuins/genetics ; Sirtuins/metabolism
    Chemical Substances Interleukins ; Sirtuins (EC 3.5.1.-)
    Language English
    Publishing date 2023-03-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24065157
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  7. Article ; Online: Pathogenetic and clinical study of a patient with thrombocytopenia due to the p.E527K gain-of-function variant of SRC.

    Barozzi, Serena / Di Buduo, Christian A / Marconi, Caterina / Bozzi, Valeria / Seri, Marco / Romano, Francesca / Balduini, Alessandra / Pecci, Alessandro

    Haematologica

    2021  Volume 106, Issue 3, Page(s) 918–922

    MeSH term(s) Anemia ; Gain of Function Mutation ; Humans ; Leukopenia ; Thrombocytopenia/diagnosis ; Thrombocytopenia/genetics
    Language English
    Publishing date 2021-03-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2020.268516
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  8. Article ; Online: Mechanisms of platelet release:

    Abbonante, Vittorio / Di Buduo, Christian A / Malara, Alessandro / Laurent, Pierre-Alexandre / Balduini, Alessandra

    Platelets

    2020  Volume 31, Issue 6, Page(s) 717–723

    Abstract: Mechanisms related to platelet release in the context of the bone marrow niche are not completely known. In this review we discuss what has been discovered about four critical aspects of this process: 1) the bone marrow niche organization, 2) the role of ...

    Abstract Mechanisms related to platelet release in the context of the bone marrow niche are not completely known. In this review we discuss what has been discovered about four critical aspects of this process: 1) the bone marrow niche organization, 2) the role of the extracellular matrix components, 3) the mechanisms by which megakaryocytes release platelets and 4) the novel approaches to mimic the bone marrow environment and produce platelets
    MeSH term(s) Animals ; Blood Platelets/metabolism ; Humans
    Language English
    Publishing date 2020-06-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2020.1774532
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    Zs.A 2888: Show issues Location:
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  9. Article ; Online: Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.

    Marín-Quílez, Ana / Díaz-Ajenjo, Lorena / Di Buduo, Christian A / Zamora-Cánovas, Ana / Lozano, María Luisa / Benito, Rocío / González-Porras, José Ramón / Balduini, Alessandra / Rivera, José / Bastida, José María

    International journal of molecular sciences

    2023  Volume 24, Issue 6

    Abstract: Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is ... ...

    Abstract Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance. Platelets have a half-life in blood ranging from 8 to 11 days, after which they lose the final sialic acid and are recognized by receptors in the liver and eliminated from the bloodstream. This favors the transduction of thrombopoietin, which induces megakaryopoiesis to produce new platelets. More than two hundred enzymes are responsible for proper glycosylation and sialylation. In recent years, novel disorders of glycosylation caused by molecular variants in multiple genes have been described. The phenotype of the patients with genetic alterations in
    MeSH term(s) Humans ; Glycosylation ; Thrombocytopenia/etiology ; Blood Platelets/metabolism ; Megakaryocytes/metabolism ; Thrombopoiesis ; Thrombopoietin ; Nucleotide Transport Proteins/metabolism
    Chemical Substances Thrombopoietin (9014-42-0) ; SLC35A1 protein, human ; Nucleotide Transport Proteins
    Language English
    Publishing date 2023-03-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24065109
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  10. Article ; Online: Increased B4GALT1 expression is associated with platelet surface galactosylation and thrombopoietin plasma levels in MPNs.

    Di Buduo, Christian A / Giannini, Silvia / Abbonante, Vittorio / Rosti, Vittorio / Hoffmeister, Karin M / Balduini, Alessandra

    Blood

    2020  Volume 137, Issue 15, Page(s) 2085–2089

    Abstract: Aberrant megakaryopoiesis is a hallmark of the myeloproliferative neoplasms (MPNs), a group of clonal hematological malignancies originating from hematopoietic stem cells, leading to an increase in mature blood cells in the peripheral blood. Sialylated ... ...

    Abstract Aberrant megakaryopoiesis is a hallmark of the myeloproliferative neoplasms (MPNs), a group of clonal hematological malignancies originating from hematopoietic stem cells, leading to an increase in mature blood cells in the peripheral blood. Sialylated derivatives of the glycan structure β4-N-acetyllactosamine (Galβ1,4GlcNAc or type-2 LacNAc, hereafter referred to as LacNAc) regulate platelet life span, hepatic thrombopoietin (TPO) production, and thrombopoiesis. We found increased TPO plasma levels in MPNs with high allele burden of the mutated clones. Remarkably, platelets isolated from MPNs had a significant increase in LacNAc expression that correlated with the high allele burden regardless of the underlying identified mutation. Megakaryocytes derived in vitro from these patients showed an increased expression of the B4GALT1 gene encoding β-1,4-galactosyltransferase 1 (β4GalT1). Consistently, megakaryocytes from MPN showed increased LacNAc expression relative to healthy controls, which was counteracted by the treatment with a Janus kinase 1/2 inhibitor. Altered expression of B4GALT1 in mutant megakaryocytes can lead to the production of platelets with aberrant galactosylation, which in turn promote hepatic TPO synthesis regardless of platelet mass. Our findings provide a new paradigm for understanding aberrant megakaryopoiesis in MPNs and identify β4GalT1 as a potential actionable target for therapy.
    MeSH term(s) Blood Platelets/metabolism ; Blood Platelets/pathology ; Galactose/analysis ; Galactose/metabolism ; Galactosyltransferases/genetics ; Galactosyltransferases/metabolism ; Humans ; Megakaryocytes/metabolism ; Megakaryocytes/pathology ; Mutation ; Myeloproliferative Disorders/blood ; Myeloproliferative Disorders/genetics ; Myeloproliferative Disorders/metabolism ; Thrombopoietin/blood ; Thrombopoietin/metabolism ; Up-Regulation
    Chemical Substances Thrombopoietin (9014-42-0) ; Galactosyltransferases (EC 2.4.1.-) ; beta-1,4-galactosyltransferase I (EC 2.4.1.-) ; Galactose (X2RN3Q8DNE)
    Language English
    Publishing date 2020-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2020007265
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    Zs.MO 364: Show issues

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