{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:08:49Z","timestamp":1791950929351,"version":"4.3.4"},"reference-count":113,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NHLBI","award":["HL 158670"],"award-info":[{"award-number":["HL 158670"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Megakaryocytes (MKs), which primarily develop in bone marrow (BM) from hematopoietic stem cells, are critical for platelet production. Beyond their well-established role in thrombopoiesis, MKs have been identified as important for BM niche maintenance, such as by supporting the growth and differentiation of other cell types. Recently, megakaryopoiesis has been reported as yielding divergent subpopulations of MKs, as evidenced by single-cell RNA sequencing of lung, spleen, or BM resident MKs. Interestingly, these subpopulations constitute a significant proportion of \u201cimmune MKs\u201d expressing various classical immune markers and capable of phagocytosing pathogens and contributing to antigen presentation. As such, MKs were also found to regulate inflammation, mainly by secreting various cytokines and chemokines to crosstalk with other cell types. The level and functional signature of these \u201cimmune MKs\u201d were found to be altered in various pathological conditions, indicative of their purposeful values in health and diseases. In this review, we survey and highlight newly reported functional immune and inflammatory properties of MKs in health and in select pathologies.<\/jats:p>","DOI":"10.3390\/cells14141053","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:38:27Z","timestamp":1752140307000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immune and Inflammatory Properties of Megakaryocytes"],"prefix":"10.3390","volume":"14","author":[{"given":"Shiv Vardan","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Medicine, Whitaker Cardiovascular Institute, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Lucerne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Whitaker Cardiovascular Institute, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-3024","authenticated-orcid":false,"given":"Katya","family":"Ravid","sequence":"additional","affiliation":[{"name":"Department of Medicine, Whitaker Cardiovascular Institute, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1538-7836.2011.04364.x","article-title":"Regulating thrombus growth and stability to achieve an optimal response to injury","volume":"9","author":"Brass","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/bjh.12758","article-title":"Interpreting the developmental dance of the megakaryocyte: A review of the cellular and molecular processes mediating platelet formation","volume":"165","author":"Machlus","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1365-2141.2006.06215.x","article-title":"Megakaryocyte development and platelet production","volume":"134","author":"Deutsch","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jcp.10035","article-title":"Roads to polyploidy: The megakaryocyte example","volume":"190","author":"Ravid","year":"2002","journal-title":"J. Cell. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-4419-6199-0_7","article-title":"Polyploidy: Mechanisms and cancer promotion in hematopoietic and other cells","volume":"676","author":"Nguyen","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100158","DOI":"10.1016\/j.rpth.2023.100158","article-title":"Spatial transcriptomics of murine bone marrow megakaryocytes at single-cell resolution","volume":"7","author":"Tilburg","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/jth.15271","article-title":"Transcriptional characterization of human megakaryocyte polyploidization and lineage commitment","volume":"19","author":"Choudry","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00018-014-1813-y","article-title":"The secret life of a megakaryocyte: Emerging roles in bone marrow homeostasis control","volume":"72","author":"Malara","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00212","DOI":"10.1097\/BS9.0000000000000212","article-title":"Versatility of megakaryocytes in homeostasis and disease","volume":"6","author":"Wang","year":"2024","journal-title":"Blood Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1186\/s13287-024-03966-z","article-title":"iPSC-derived megakaryocytes and platelets accelerate wound healing and angiogenesis","volume":"15","author":"Kosaka","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.thromres.2009.11.004","article-title":"The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes","volume":"125","author":"Beaulieu","year":"2010","journal-title":"Thromb. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.exphem.2005.06.012","article-title":"Hematopoiesis in the yolk sac: More than meets the eye","volume":"33","author":"McGrath","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15283\/ijsc19127","article-title":"Hematopoietic stem cells and their roles in tissue regeneration","volume":"13","author":"Lee","year":"2020","journal-title":"Int. J. Stem Cells"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mann, Z., Sengar, M., Verma, Y.K., Rajalingam, R., and Raghav, P.K. (2022). Hematopoietic stem cell factors: Their functional role in self-renewal and clinical aspects. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.664261"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1182\/blood-2015-07-607945","article-title":"Hematopoietic stem\/progenitor cell commitment to the megakaryocyte lineage","volume":"127","author":"Woolthuis","year":"2016","journal-title":"Blood."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/ncb3493","article-title":"Human haematopoietic stem cell lineage commitment is a continuous process","volume":"19","author":"Velten","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.devcel.2017.03.020","article-title":"Hematopoiesis lineage tree uprooted: Every cell is a rainbow","volume":"41","author":"Hirschi","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11075","DOI":"10.1038\/ncomms11075","article-title":"Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells","volume":"7","author":"Grover","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/rth2.12129","article-title":"Genomics and transcriptomics of megakaryocytes and platelets: Implications for health and disease","volume":"2","author":"Fisher","year":"2018","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.immuni.2024.02.006","article-title":"Differentiation route determines the functional outputs of adult megakaryopoiesis","volume":"57","author":"Li","year":"2024","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.stem.2015.07.007","article-title":"Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors","volume":"17","author":"Haas","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2008.01.025","article-title":"Hematopoiesis: An evolving paradigm for stem cell biology","volume":"132","author":"Orkin","year":"2008","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1242\/dev.083147","article-title":"Hematopoiesis","volume":"140","author":"Zon","year":"2013","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.molcel.2020.04.008","article-title":"Single-cell analyses reveal megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets","volume":"78","author":"Psaila","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1182\/blood-2010-08-303537","article-title":"The replication rate of human hematopoietic stem cells in vivo","volume":"117","author":"Catlin","year":"2011","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1182\/blood.V96.10.3399","article-title":"In vivo kinetics of murine hemopoietic stem cells","volume":"96","author":"Abkowitz","year":"2000","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1038\/s41467-023-37780-7","article-title":"High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production","volume":"14","author":"Heazlewood","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.4161\/cc.10.10.15619","article-title":"Thrombopoietin and hematopoietic stem cells","volume":"10","author":"Metcalf","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1182\/bloodadvances.2021005977","article-title":"Megakaryocyte\/platelet-derived TGF-beta1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver","volume":"6","author":"Gostynska","year":"2022","journal-title":"Blood Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1111\/jth.15024","article-title":"Megakaryocytes use in vivo podosome-like structures working collectively to penetrate the endothelial barrier of bone marrow sinusoids","volume":"18","author":"Eckly","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1538-7836.2011.04571.x","article-title":"Megakaryocytes, malignancy and bone marrow vascular niches","volume":"10","author":"Psaila","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1161\/ATVBAHA.119.312129","article-title":"New insights into the differentiation of megakaryocytes from hematopoietic progenitors","volume":"39","author":"Noetzli","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1182\/blood.V3.8.934.934","article-title":"The significance of megakaryocytes in the peripheral circulation","volume":"3","author":"Whitby","year":"1948","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1055\/s-0044-1787752","article-title":"Clinical and molecular characteristics of megakaryocytes in myelodysplastic syndrome","volume":"11","author":"Luo","year":"2024","journal-title":"Glob. Med. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100197","DOI":"10.1016\/j.rpth.2023.100197","article-title":"Inside-to-outside and back to the future of megakaryopoiesis","volume":"7","author":"Miguel","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2206918","DOI":"10.1080\/09537104.2023.2206918","article-title":"N-methyl-D-aspartate receptor regulates the circadian clock in megakaryocytic cells and impacts cell proliferation through BMAL1","volume":"34","author":"Hearn","year":"2023","journal-title":"Platelets"},{"key":"ref_37","first-page":"212","article-title":"Megakaryocytes in peripheral blood smears","volume":"36","author":"Garg","year":"2019","journal-title":"Turk. J. Haematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/JLB.MR0718-261RR","article-title":"Megakaryocytes as immune cells","volume":"105","author":"Cunin","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41417-022-00476-z","article-title":"Global characterization of megakaryocytes in bone marrow, peripheral blood, and cord blood by single-cell RNA sequencing","volume":"29","author":"Zhang","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1182\/blood-2002-02-0490","article-title":"The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells","volume":"100","author":"Slayton","year":"2002","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e153920","DOI":"10.1172\/JCI153920","article-title":"Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression","volume":"132","author":"Valet","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1172\/JCI84538","article-title":"Neutrophil extracellular traps-the dark side of neutrophils","volume":"126","author":"Sorensen","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e186111","DOI":"10.1172\/JCI186111","article-title":"The lung is a megakaryocyte outpost that can defend against thrombocytopenic attack","volume":"134","author":"Yeung","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1084\/jem.65.2.177","article-title":"The production of blood platelets in the lungs","volume":"65","author":"Howell","year":"1937","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1182\/blood.V26.6.720.720","article-title":"Circulating megakaryocytes and platelet release in the lung","volume":"26","author":"Kaufman","year":"1965","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1080\/09537104.2019.1708885","article-title":"Use of electron microscopy to study megakaryocytes","volume":"31","author":"Scandola","year":"2020","journal-title":"Platelets"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1182\/bloodadvances.2020002843","article-title":"Lung megakaryocytes display distinct transcriptional and phenotypic properties","volume":"4","author":"Yeung","year":"2020","journal-title":"Blood Adv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e181111","DOI":"10.1172\/JCI181111","article-title":"Long-lived lung megakaryocytes contribute to platelet recovery in thrombocytopenia models","volume":"134","author":"Livada","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature21706","article-title":"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors","volume":"544","author":"Caudrillier","year":"2017","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1182\/blood.2021010697","article-title":"Single-cell analysis of ploidy and the transcriptome reveals functional and spatial divergency in murine megakaryopoiesis","volume":"138","author":"Sun","year":"2021","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Khatib-Massalha, E., and Mendez-Ferrer, S. (2022). Megakaryocyte diversity in ontogeny, functions and cell-cell interactions. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.840044"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00428-020-02926-1","article-title":"Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: An autopsy study with clinical correlation and review of the literature","volume":"478","author":"Salas","year":"2021","journal-title":"Virchows Arch. Int. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1007\/s11684-024-1087-1","article-title":"Immunological face of megakaryocytes","volume":"18","author":"Li","year":"2024","journal-title":"Front. Med."},{"key":"ref_54","first-page":"512","article-title":"Expression of Fc gamma RII and CD4 receptors by normal human megakaryocytes","volume":"20","author":"Gewirtz","year":"1992","journal-title":"Exp. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1055\/s-0038-1650339","article-title":"Characterization of Fc gamma receptors on human megakaryocytes","volume":"75","author":"Wu","year":"1996","journal-title":"Thromb. Haemost."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/ejh.12528","article-title":"Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia","volume":"95","author":"Arnold","year":"2015","journal-title":"Eur. J. Haematol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Mathur, M., Chan, T.M., Oh, K.H., Kooienga, L., Zhuo, M., Pinto, C.S., and Chacko, B. (2023). A proliferation-inducing ligand (april) in the pathogenesis of immunoglobulin a nephropathy: A Review of the Evidence. J. Clin. Med., 12.","DOI":"10.3390\/jcm12216927"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Xu, F., Wang, G., Zhao, F., Huang, Y., Fan, Z., Mei, S., Xie, Y., Wei, L., Hu, Y., and Wang, C. (2022). IFITM3 Inhibits SARS-CoV-2 Infection and Is Associated with COVID-19 Susceptibility. Viruses, 14.","DOI":"10.3390\/v14112553"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cels.2020.02.006","article-title":"Engineered fluorescent E. coli lysogens allow live-cell imaging of functional prophage induction triggered inside macrophages","volume":"10","author":"Bodner","year":"2020","journal-title":"Cell Syst."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5970","DOI":"10.4049\/jimmunol.1200452","article-title":"Megakaryocyte progenitors are the main APCs inducing Th17 response to lupus autoantigens and foreign antigens","volume":"188","author":"Kang","year":"2012","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.thromres.2004.03.023","article-title":"Expression of Toll-like receptors on human platelets","volume":"113","author":"Shiraki","year":"2004","journal-title":"Thromb. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1182\/bloodadvances.2017007021","article-title":"Mature murine megakaryocytes present antigen-MHC class I molecules to T cells and transfer them to platelets","volume":"1","author":"Zufferey","year":"2017","journal-title":"Blood Adv."},{"key":"ref_63","first-page":"15","article-title":"Unraveling mechanisms that control platelet production","volume":"39","author":"Italiano","year":"2013","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1182\/blood-2024-205355","article-title":"Platelet factor 4 (PF4) regulates hematopoietic stem cell aging","volume":"114","author":"Zhang","year":"2024","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"De Wispelaere, K., and Freson, K. (2022). The analysis of the human megakaryocyte and platelet coding transcriptome in healthy and diseased subjects. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147647"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.4049\/jimmunol.139.9.2915","article-title":"Role of natural killer cells, in comparison with T lymphocytes and monocytes, in the regulation of normal human megakaryocytopoiesis in vitro","volume":"139","author":"Gewirtz","year":"1987","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1182\/blood.V51.2.245.245","article-title":"Regulation of megakaryopoiesis in long-term murine bone marrow cultures","volume":"51","author":"Williams","year":"1978","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1182\/bloodadvances.2024015621","article-title":"Mature Megakaryocytes Acquire Immune Characteristics in a Mouse Model of Aplastic Anemia","volume":"9","author":"Prabahran","year":"2025","journal-title":"Blood Adv."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1182\/blood.V52.1.163.163","article-title":"Regulation of proliferation of murine megakaryocyte progenitor cells by cell cycle","volume":"52","author":"Williams","year":"1978","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1182\/blood-2006-08-038901","article-title":"Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2","volume":"109","author":"Chen","year":"2007","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eabo5224","DOI":"10.1126\/sciadv.abo5224","article-title":"Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer","volume":"8","author":"Roweth","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eadd7564","DOI":"10.1126\/science.add7564","article-title":"Yolk sac cell atlas reveals multiorgan functions during human early development","volume":"381","author":"Goh","year":"2023","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1182\/blood.2020009301","article-title":"Fetal vs adult megakaryopoiesis","volume":"139","author":"Davenport","year":"2022","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.molimm.2009.09.012","article-title":"Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival","volume":"47","author":"Lattin","year":"2009","journal-title":"Mol. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1080\/09537104.2020.1742879","article-title":"Changes in megakaryopoiesis over ontogeny and their implications in health and disease","volume":"31","author":"Davenport","year":"2020","journal-title":"Platelets"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41467-017-00201-7","article-title":"Thrombopoiesis is spatially regulated by the bone marrow vasculature","volume":"8","author":"Stegner","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.stem.2022.07.004","article-title":"Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets","volume":"29","author":"Qin","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"100184","DOI":"10.1016\/j.rpth.2023.100184","article-title":"Regulation of megakaryo\/thrombopoiesis by endosomal toll-like receptor 7 and 8 activation of CD34(+) cells in a viral infection model","volume":"7","author":"Rodriguez","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1172\/JCI26720","article-title":"Megakaryocyte biology and related disorders","volume":"115","author":"Pang","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1634\/stemcells.19-5-397","article-title":"Molecular and transcriptional regulation of megakaryocyte differentiation","volume":"19","author":"Shivdasani","year":"2001","journal-title":"Stem Cells."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/MOH.0000000000000669","article-title":"Still a burning question: The interplay between inflammation and fibrosis in myeloproliferative neoplasms","volume":"28","author":"Gleitz","year":"2021","journal-title":"Curr. Opin. Hematol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.stem.2013.06.009","article-title":"Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche","volume":"13","author":"Schepers","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.cellsig.2005.09.010","article-title":"Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR in TPO-dependent cell lines and primary megakaryocytes","volume":"18","author":"Chanprasert","year":"2006","journal-title":"Cell. Signal."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"100005","DOI":"10.1016\/j.cytox.2019.100005","article-title":"Cytokines frequently implicated in myeloproliferative neoplasms","volume":"1","author":"Wang","year":"2019","journal-title":"Cytokine X"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chen, B., Mu, C., Zhang, Z., He, X., and Liu, X. (2022). The love-hate relationship between tgf-beta signaling and the immune system during development and tumorigenesis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.891268"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1177\/11297298231192386","article-title":"Functions for platelet factor 4 (PF4\/CXCL4) and its receptors in fibroblast-myofibroblast transition and fibrotic failure of arteriovenous fistulas (AVFs)","volume":"25","author":"Xiao","year":"2024","journal-title":"J. Vasc. Access"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"453020","DOI":"10.1155\/2015\/453020","article-title":"Proinflammatory cytokine IL-6 and JAK-STAT signaling pathway in myeloproliferative neoplasms","volume":"2015","author":"Cokic","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.1182\/bloodadvances.2022009022","article-title":"Circulating SARS-CoV-2+ megakaryocytes are associated with severe viral infection in COVID-19","volume":"7","author":"Fortmann","year":"2023","journal-title":"Blood Adv."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00018-022-04318-x","article-title":"Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19","volume":"79","author":"Zhu","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"100434","DOI":"10.1016\/j.eclinm.2020.100434","article-title":"Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series","volume":"24","author":"Rapkiewicz","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Pannone, G., Pedicillo, M.C., De Stefano, I.S., Angelillis, F., Barile, R., Pannone, C., Villani, G., Miele, F., Municin\u00f2, M., and Ronchi, A. (2024). The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Lung Megakaryocyte Up-Regulation in the Microthrombosis Mechanism. Cells, 13.","DOI":"10.3390\/cells13100854"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Bermejo-Jambrina, M., Eder, J., Helgers, L.C., Hertoghs, N., Nijmeijer, B.M., Stunnenberg, M., and Geijtenbeek, T.B.H. (2018). C-type lectin receptors in antiviral immunity and viral escape. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00590"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7396","DOI":"10.1038\/s41467-024-51686-y","article-title":"Lung megakaryocytes engulf inhaled airborne particles to promote intrapulmonary inflammation and extrapulmonary distribution","volume":"15","author":"Qiu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e137377","DOI":"10.1172\/JCI137377","article-title":"Lung megakaryocytes are immune modulatory cells","volume":"131","author":"Pariser","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e78662","DOI":"10.7554\/eLife.78662","article-title":"CXCR4(high) megakaryocytes regulate host-defense immunity against bacterial pathogens","volume":"11","author":"Wang","year":"2022","journal-title":"eLife"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s00018-024-05150-1","article-title":"MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model","volume":"81","author":"Zhu","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.exphem.2004.11.015","article-title":"MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells","volume":"33","author":"Oba","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Niu, C., Liang, T., Chen, Y., Zhu, S., Zhou, L., Chen, N., Qian, L., Wang, Y., Li, M., and Zhou, X. (2024). SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1444643"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1182\/bloodadvances.2023012367","article-title":"SARS-CoV-2 infection modifies the transcriptome of the megakaryocytes in the bone marrow","volume":"8","author":"Allaeys","year":"2024","journal-title":"Blood Adv."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"155934","DOI":"10.1016\/j.cyto.2022.155934","article-title":"Inflammasomes and IL-1 family cytokines in SARS-CoV-2 infection: From prognostic marker to therapeutic agent","volume":"157","author":"Declercq","year":"2022","journal-title":"Cytokine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00018-017-2641-7","article-title":"Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property","volume":"75","author":"Wang","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5537","DOI":"10.1172\/JCI129502","article-title":"\u03b22 adrenergic receptor-mediated signaling regulates the immunosuppressive potential of myeloid-derived suppressor cells","volume":"129","author":"Mohammadpour","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e124213","DOI":"10.1172\/jci.insight.124213","article-title":"Aged marrow macrophages expand platelet-biased hematopoietic stem cells via Interleukin1B","volume":"5","author":"Frisch","year":"2019","journal-title":"JCI Insight"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e132727","DOI":"10.1172\/JCI132727","article-title":"mTOR-dependent translation amplifies microglia priming in aging mice","volume":"131","author":"Keane","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00018-022-04356-5","article-title":"Mechanisms involved in hematopoietic stem cell aging","volume":"79","author":"Fujino","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1186\/s13054-024-05221-6","article-title":"Megakaryocyte in sepsis: The trinity of coagulation, inflammation and immunity","volume":"28","author":"Hua","year":"2024","journal-title":"Crit. Care"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Garcia, C., Compagnon, B., Poette, M., Gratacap, M.P., Lapebie, F.X., Voisin, S., Minville, V., Payrastre, B., Vardon-Bounes, F., and Ribes, A. (2022). Platelet versus megakaryocyte: Who is the real bandleader of thromboinflammation in sepsis?. Cells, 11.","DOI":"10.3390\/cells11091507"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1213\/ANE.0000000000006888","article-title":"Sepsis-induced coagulopathy: A comprehensive narrative review of pathophysiology, clinical presentation, diagnosis, and management strategies","volume":"138","author":"Williams","year":"2024","journal-title":"Anesth. Analg."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.bjid.2015.10.011","article-title":"TLR2 and TLR4 mediated host immune responses in major infectious diseases: A review","volume":"20","author":"Mukherjee","year":"2016","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Tominari, T., Matsumoto, C., Tanaka, Y., Shimizu, K., Takatoya, M., Sugasaki, M., Karouji, K., Kasuga, U., Miyaura, C., and Miyata, S. (2024). Roles of toll-like receptor signaling in inflammatory bone resorption. Biology, 13.","DOI":"10.3390\/biology13090692"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-015-0152-2","article-title":"Angptl4 is upregulated under inflammatory conditions in the bone marrow of mice, expands myeloid progenitors, and accelerates reconstitution of platelets after myelosuppressive therapy","volume":"8","author":"Schumacher","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1161\/ATVBAHA.120.314644","article-title":"Platelet Extracellular Vesicles: Beyond the Blood","volume":"41","author":"Puhm","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1182\/blood.2023020895","article-title":"The bone marrow is the primary site of thrombopoiesis","volume":"143","author":"Asquith","year":"2024","journal-title":"Blood"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/14\/1053\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:40Z","timestamp":1760033260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/14\/1053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":113,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cells14141053"],"URL":"https:\/\/doi.org\/10.3390\/cells14141053","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}