{"doi":"10.1038/s41586-024-07671-y","title":"Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis","abstract":"<jats:title>Abstract</jats:title><jats:p>Platelet homeostasis is essential for vascular integrity and immune defence<jats:sup>1,2</jats:sup>. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear<jats:sup>3,4</jats:sup>. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection<jats:sup>5</jats:sup>. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.</jats:p>","journal":"Nature","year":2024,"id":670108,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":1,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":71399,"name":"Hellen Ishikawa‐Ankerhold","orcid":"0000-0003-0307-7022","position":1,"is_corresponding":false},{"id":1750208,"name":"Susanne Stutte","orcid":null,"position":2,"is_corresponding":false},{"id":1750210,"name":"Wenwen Fu","orcid":null,"position":3,"is_corresponding":false},{"id":1750213,"name":"Jutta Weitz","orcid":null,"position":4,"is_corresponding":false},{"id":998404,"name":"Anne Dueck","orcid":"0000-0002-7956-6327","position":5,"is_corresponding":false},{"id":1750215,"name":"Bhavishya Nelakuditi","orcid":null,"position":6,"is_corresponding":false},{"id":814551,"name":"Valeria Fumagalli","orcid":"0000-0003-2583-2498","position":7,"is_corresponding":false},{"id":1750217,"name":"Dominic van den Heuvel","orcid":"0000-0002-8998-0396","position":8,"is_corresponding":false},{"id":1750219,"name":"Larissa Belz","orcid":null,"position":9,"is_corresponding":false},{"id":1750220,"name":"Gulnoza Sobirova","orcid":null,"position":10,"is_corresponding":false},{"id":1220387,"name":"Zhe Zhang","orcid":"0000-0002-4771-0697","position":11,"is_corresponding":false},{"id":1750221,"name":"Anna Titova","orcid":null,"position":12,"is_corresponding":false},{"id":1750222,"name":"Alejandro Martinez Navarro","orcid":"0000-0003-3893-1719","position":13,"is_corresponding":false},{"id":1750223,"name":"Kami Pekayvaz","orcid":null,"position":14,"is_corresponding":false},{"id":92020,"name":"Michael Lorenz","orcid":"0000-0002-7881-8027","position":15,"is_corresponding":false},{"id":1357000,"name":"Louisa von Baumgarten","orcid":"0000-0002-6634-0927","position":16,"is_corresponding":false},{"id":34845,"name":"Jan Kranich","orcid":"0000-0002-9928-4132","position":17,"is_corresponding":false},{"id":64730,"name":"Tobias Straub","orcid":"0000-0002-0547-0453","position":18,"is_corresponding":false},{"id":1750224,"name":"Bastian Popper","orcid":null,"position":19,"is_corresponding":false},{"id":583330,"name":"Vanessa Zheden","orcid":"0000-0002-9438-4783","position":20,"is_corresponding":false},{"id":1750225,"name":"Walter Anton Kaufmann","orcid":null,"position":21,"is_corresponding":false},{"id":1750226,"name":"Chenglong Guo","orcid":null,"position":22,"is_corresponding":false},{"id":40344,"name":"Guido Piontek","orcid":null,"position":23,"is_corresponding":false},{"id":57943,"name":"Saskia von Stillfried","orcid":"0000-0002-5260-8494","position":24,"is_corresponding":false},{"id":57985,"name":"Peter Boor","orcid":"0000-0001-9921-4284","position":25,"is_corresponding":false},{"id":71132,"name":"Marco Colonna","orcid":"0000-0001-5222-4987","position":26,"is_corresponding":false},{"id":75478,"name":"Sebastian Clauss","orcid":"0000-0002-5675-6128","position":27,"is_corresponding":false},{"id":314985,"name":"Christian Schulz","orcid":"0000-0002-8149-0747","position":28,"is_corresponding":false},{"id":34853,"name":"Thomas Brocker","orcid":"0000-0001-7060-5433","position":29,"is_corresponding":false},{"id":1750227,"name":"Barbara Walzog","orcid":"0000-0001-7729-6565","position":30,"is_corresponding":false},{"id":842271,"name":"Christoph Scheiermann","orcid":"0000-0002-9212-0995","position":31,"is_corresponding":false},{"id":400805,"name":"William C. Aird","orcid":null,"position":32,"is_corresponding":false},{"id":78272,"name":"Claus Nerlov","orcid":"0000-0002-0544-735X","position":33,"is_corresponding":false},{"id":598698,"name":"Konstantin Stark","orcid":"0000-0002-5369-8399","position":34,"is_corresponding":false},{"id":1685250,"name":"Tobias Petzold","orcid":null,"position":35,"is_corresponding":false},{"id":65579,"name":"Stefan Engelhardt","orcid":"0000-0001-5378-8661","position":36,"is_corresponding":false},{"id":25226,"name":"Michael Sixt","orcid":"0000-0002-6620-9179","position":37,"is_corresponding":false},{"id":1507360,"name":"Robert Hauschild","orcid":"0000-0001-9843-3522","position":38,"is_corresponding":false},{"id":601466,"name":"Martina Rudelius","orcid":null,"position":39,"is_corresponding":false},{"id":21015,"name":"Robert A. J. Oostendorp","orcid":"0000-0002-4947-0412","position":40,"is_corresponding":false},{"id":52959,"name":"Matteo Iannacone","orcid":"0000-0002-9370-2671","position":41,"is_corresponding":false},{"id":3349,"name":"Matthias Heinig","orcid":"0000-0002-5612-1720","position":42,"is_corresponding":false},{"id":548598,"name":"Steffen Maßberg","orcid":"0000-0001-7387-3986","position":43,"is_corresponding":false},{"id":1750207,"name":"Florian Gaertner","orcid":"0000-0001-6120-3723","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis","abstract":"<jats:title>Abstract</jats:title><jats:p>Platelet homeostasis is essential for vascular integrity and immune defence<jats:sup>1,2</jats:sup>. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear<jats:sup>3,4</jats:sup>. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection<jats:sup>5</jats:sup>. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.</jats:p>","is_dataset_classified":null,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"datacite_reuse_total":1,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38987596","pmcid":"PMC11254756","openalex_id":"https://openalex.org/W4400491938","authors":[],"funders":[{"funder_name":"European Research Council","grant_id":"101001791","title":"AI-augmented, Multiscale Image-based Diagnostics  of Chronic Kidney Disease"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"210592381/SFB 1054","title":"Control and Plasticity of Cell-Fate Decisions in the Immune System"},{"funder_name":"European Commission","grant_id":"747687","title":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"},{"funder_name":"European Commission","grant_id":"833440","title":"Cross-talk between platelets and immunity - implications for host homeostasis and defense"},{"funder_name":"European Commission","grant_id":"101078110","title":"Cell mechanics of megakaryocytes in 3D tissues - deciphering mechanobiology of platelet formation"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"165054336/SFB 914","title":"Trafficking of Immune Cells in Inflammation, Development and Disease"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"238187445/SFB 1123","title":"Atherosclerosis: Mechanisms and Networks of Novel Therapeutic Targets"}],"total_grants":7,"fwci":11.3491,"citation_percentile":0.99009013,"influential_citations":0,"citation_trend":[{"year":2024,"count":4},{"year":2025,"count":25},{"year":2026,"count":10}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41586-024-07671-y.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41586-024-07671-y.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41586-024-07671-y","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41586-024-07671-y","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38987596","host_type":"repository"},{"url":"https://ora.ox.ac.uk/objects/uuid:9880de9d-90bc-4014-82d6-3e18361c7776","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11254756","host_type":"repository"},{"url":"https://digitalcommons.library.tmc.edu/uthgsbs_docs/1578","host_type":"repository"},{"url":"https://digitalcommons.wustl.edu/oa_4/4089","host_type":"repository"},{"url":"https://epub.ub.uni-muenchen.de/121884/","host_type":"journal"},{"url":"https://mediatum.ub.tum.de/1758785","host_type":"repository"},{"url":"https://push-zb.helmholtz-munich.de/frontdoor.php?source_opus=71094","host_type":"repository"},{"url":"https://archive-ouverte.unige.ch/unige:182185","host_type":"repository"},{"url":"https://doi.org/10.18154/rwth-conv-253655","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11254756","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11254756?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.18154/rwth-conv-253655","host_type":""},{"url":"http://dx.doi.org/10.1038/s41586-024-07671-y","host_type":""},{"url":"https://hdl.handle.net/20.500.11768/175356","host_type":""},{"url":"https://publications.rwth-aachen.de/record/1007301","host_type":""},{"url":"http://dx.doi.org/10.18154/RWTH-CONV-253655","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/s41586-024-07671-y","host_type":""}],"fields_of_study":["Platelet Disorders and Treatments","Immune Cell Function and Interaction","T-cell and B-cell Immunology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Female","Humans","Male","Mice","Apoptosis","Blood Platelets","Bone Marrow","Cell Lineage","Cell Proliferation","Dendritic Cells","Feedback, Physiological","Homeostasis","Immunity, Innate","Intravital Microscopy","Megakaryocytes","Mice, Inbred C57BL","SARS-CoV-2","Thrombopoiesis","COVID-19"],"mesh_terms":["Intravital Microscopy","COVID-19","SARS-CoV-2","Animals","Blood Platelets","Bone Marrow","Dendritic Cells","Female","Homeostasis","Humans","Immunity, Innate","Male","Megakaryocytes","Mice, Inbred C57BL","Interferon-alpha","Apoptosis","Cell Lineage","Feedback, Physiological","Thrombopoiesis","Cell Proliferation","Mice"],"keywords":["Thrombopoiesis","Homeostasis","Cell biology","Progenitor cell","Biology","Immune system","Stem cell","Progenitor","Megakaryocyte","Immunology","Neuroscience","Male","COVID-19 / virology","Medical Sciences","Intravital Microscopy","Diseases","Apoptosis","Inbred C57BL","Mice","Bone Marrow","Medical Specialties","Medicine and Health Sciences","Innate","Feedback, Physiological","Oncology","Female","Megakaryocytes","Blood Platelets","570","Blood Platelets / cytology","Bioinformatics","Megakaryocytes / cytology","Physiological","Dendritic Cells / cytology","610","COVID-19 / physiopathology","616.07","Article","Biomedical Informatics","Feedback","Hemic and Lymphatic Diseases","COVID-19 / immunology","616","Dendritic Cells / immunology","Animals","Humans","Cell Lineage","Cell Proliferation","Megakaryocytes / immunology","SARS-CoV-2","Immunity","ICTS (Institute of Clinical and Translational Sciences)","COVID-19","Dendritic Cells","Immunity, Innate","Mice, Inbred C57BL","SARS-CoV-2 / immunology"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.18154/rwth-conv-253655","title":"Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis","publisher":"RWTH Aachen University","resource_type":"Text"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T20:15:43.575117Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}