{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:42:54Z","timestamp":1792827774846,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201018\u2010CE14\u20100037"],"award-info":[{"award-number":["ANR\u201018\u2010CE14\u20100037"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["AIRC IG 2016 18700"],"award-info":[{"award-number":["AIRC IG 2016 18700"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR\u20102016\u201002363136"],"award-info":[{"award-number":["GR\u20102016\u201002363136"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL158670"],"award-info":[{"award-number":["HL158670"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32 HL007224"],"award-info":[{"award-number":["T32 HL007224"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32 HL007501"],"award-info":[{"award-number":["T32 HL007501"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1K08HG010061\u201001A1"],"award-info":[{"award-number":["1K08HG010061\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3UL1TR001085\u201004S1"],"award-info":[{"award-number":["3UL1TR001085\u201004S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH OD\/ORIP SERCA K01 OD025290"],"award-info":[{"award-number":["NIH OD\/ORIP SERCA K01 OD025290"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    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\n                    <jats:italic>Jak2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    PMF mice show significantly elevated PIEZO1 expression, compared to wild\u2010type controls. Accordingly, Mks isolated from bone marrow aspirates of\n                    <jats:italic>JAK2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    PMF patients show increased PIEZO1 expression compared to Essential Thrombocythemia. Most importantly, PIEZO1 expression in bone marrow Mks is inversely correlated with patient platelet count. The ploidy, maturation, and proplatelet formation of Mks from\n                    <jats:italic>JAK2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    PMF patients are rescued upon PIEZO1 inhibition. Together, our data suggest that PIEZO1 places a brake on Mk maturation and platelet formation in physiology, and its upregulation in PMF Mks might contribute to aggravating some hallmarks of the disease.\n                  <\/jats:p>","DOI":"10.1002\/ajh.27184","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T11:21:37Z","timestamp":1704194497000},"page":"336-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Newly identified roles for\n                    <scp>PIEZO1<\/scp>\n                    mechanosensor in controlling normal megakaryocyte development and in primary myelofibrosis"],"prefix":"10.1002","volume":"99","author":[{"given":"Vittorio","family":"Abbonante","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Department of Health Sciences Magna Graecia University of Catanzaro  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia Iris","family":"Karkempetzaki","sequence":"additional","affiliation":[{"name":"Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"School of Medicine University of Crete  Heraklion Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Leon","sequence":"additional","affiliation":[{"name":"INSERM, EFS Grand Est, BPPS UMR\u2010S 1255 Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anandi","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Institute of Immunology Stanford University School of Medicine  Palo Alto California United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"Di Buduo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Hematology Division Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Marie","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Guinard","sequence":"additional","affiliation":[{"name":"INSERM, EFS Grand Est, BPPS UMR\u2010S 1255 Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane","family":"Weber","sequence":"additional","affiliation":[{"name":"INSERM, EFS Grand Est, BPPS UMR\u2010S 1255 Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"De Acutis","sequence":"additional","affiliation":[{"name":"Interdepartmental Research Center \u201cE. Piaggio\u201d University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Vozzi","sequence":"additional","affiliation":[{"name":"Interdepartmental Research Center \u201cE. Piaggio\u201d University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0812","authenticated-orcid":false,"given":"Alessandra","family":"Iurlo","sequence":"additional","affiliation":[{"name":"Hematology Division Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katya","family":"Ravid","sequence":"additional","affiliation":[{"name":"Department of Medicine and Whitaker Cardiovascular Institute Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3145-1245","authenticated-orcid":false,"given":"Alessandra","family":"Balduini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Department of Biomedical Engineering Tufts University  Medford Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017474108"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008359"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-345876"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-699959"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.161562"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-595561"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022008680"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.22047"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.046"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21407"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.218503"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18089-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9329"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-482489"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07370"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.766196"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk1707"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15504"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23482-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-695940"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.7968"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.141283"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2017.6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-022-01293-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-019-02751-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1728752"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021015"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-064626"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.150"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-091579"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-020362"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12784"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.243113"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3791\/62511"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.2.483"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8585-2_11"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-539098"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100425"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2100105"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700885"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-339705"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000067"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-307-3_12"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07369"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.11.013"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi200770q"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1600455"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06807.x"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0054-y"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.02.007"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188356"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.152330"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158288"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2285"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-04-777417"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181074"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-06-288795"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-019-00584-5"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.06.018"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.92"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-238956"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00743-0"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.27184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T02:16:43Z","timestamp":1733278603000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.27184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,2]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/ajh.27184"],"URL":"https:\/\/doi.org\/10.1002\/ajh.27184","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,2]]},"assertion":[{"value":"2023-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}