[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-449459-105":59,"doc-detail-449459-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","the-hematopoietic-stem-cells-supportive-megakaryocytes-as-shapers-of-the-bone-marrow-niche-original-article","The hematopoietic stem cells supportive megakaryocytes as shapers of the bone marrow niche - Original Article","","Bone marrow niche integrity controls hematopoietic stem cell (HSC) fate and deteriorates with aging and in rare hematological disorders such as myelofibrosis (MF). This study examines how HSC localization and dynamics change under physiological versus pathological conditions using a newly identified HSC-supportive megakaryocyte (MK) subpopulation. Reporter mice quantified HSC distribution and nuclear GFP intensity to compare aged controls and Gata1low mutants. Supportive MK-linked HSC clusters in controls showed homogeneous GFP, whereas MF models displayed isolated, weaker GFP HSCs. Although supportive MK frequency increased in MF, their niche-maintaining function was significantly impaired, driving maladaptive remodeling, altered HSC mobilization, and hematopoietic failure.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-hematopoietic-stem-cells-supportive-megakaryocytes-as-shapers-of-the-bone-marrow-niche-original-article/449459/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-hematopoietic-stem-cells-supportive-megakaryocytes-as-shapers-of-the-bone-marrow-niche-original-article/449459.png","ImageObject",300,407,{"name":92,"@type":93},"Rainbow Cat","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-04","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does the bone marrow niche play in hematopoietic stem cells?","Question",{"text":112,"@type":113},"The bone marrow niche regulates HSC fate, and its integrity is essential for maintaining HSC function. Aging and rare diseases can significantly disrupt this niche.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were HSC localization and dynamics assessed in this study?",{"text":117,"@type":113},"The study used huCD34tTA/TetO-H2BGFP reporter mice, analyzing HSC distribution in the bone marrow and quantifying nuclear GFP intensity to evaluate repopulating potential.",{"name":119,"@type":110,"acceptedAnswer":120},"What changed in HSC-supportive megakaryocytes during myelofibrosis?",{"text":121,"@type":113},"In MF, the frequency of MKs with a supportive phenotype increased, but their ability to maintain HSCs in the niche was significantly impaired, contributing to altered HSC localization and mobilization.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},449459,1790767901,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962090769181,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","European Journal of Histochemistry 2025; volume 69:4424  \nThe hematopoietic stem cells supportive megakaryocytes as shapers of the bone marrow niche  \nFrancesca Arciprete,1 Viola Velardi,1 Paola Verachi,2 Claudio Carta,3 Antonio di Virgilio,4 Vincenzo Roberti,5 Giorgio Vivacqua,1 Rosalba Rana,1 Maria Zingariello1  \n1Unit of Microscopic and Ultrastructural Anatomy, Campus Bio Medico University of Rome; 2Department of Oncology and Molecular Medicine, Italian National Institute of Health, Rome; 3National Centre for Rare Diseases, Italian National Institute of Health, Rome 4BENA, Istituto Superiore di Sanità, Rome; 5Fondazione Policlinico Campus Bio-Medico University of Rome, Italy  \nABSTRACT  \nThe bone marrow (BM) niche plays a pivotal role in regulating the fate of hematopoietic stem cells (HSCs), and its integrity changes significantly during aging and in rare hematological disease, as in myelofibrosis (MF) . In this study, we investigated how the localization and dynamics of HSCs are influenced under physiological and pathological conditions by a newly identified by HSC-supportive megakaryocytes (MKs) subpopulation. Using huCD34tTA/TetO-H2BGFP reporter mice, we analyzed HSCs distribution within the BM and quantified nuclear green fluorescent protein (GFP) intensity to assess the repopulating potential of aged controls and mutated Gata1low mice for MF. In the control group of aged mice, cells with high levels of GFP are clustered, and adjacent to cells morphologically identifiable as supportive MKs. These clusters displayed homogeneous GFP intensity, indicating that HSCs with similar functional properties tend to co-localize in proximity to supportive MKs. By contrast, in aged huCD34/TET/Gata1low mice, GFP cells were predominantly isolated and showed reduced fluorescence intensity. Although the frequency of MKs with a supportive phenotype was increased in MF mice, analyses of GFP revealed that the ability of these MKs to maintain the HSCs in their niche was significantly impaired. Our results provide new insights on the maladaptive remodeling of the BM niche. They highlight the supportive role of MKs as potential key regulators of HSCs homeostasis. Despite their numerical expansion in MF, these cells are functionally compromised, thereby contributing to altered HSCs localization, mobilization, and to hematopoietic failure.  \nKey words: bone marrow; hematopoietic stem cells; megakaryocyte; aging; myelofibrosis; hematopoiesis.  \nCorrespondence: Maria Zingariello, Unit of Microscopic and Ultrastructural Anatomy, Campus Bio Medico University of Rome, via Alvaro del Portillo 21, 00128 Rome, Italy. E-mail: [m.zingariello@unicampus.it](m.zingariello@unicampus.it)  \n[Contributions:](Contributions: FA)[ FA](Contributions: FA), experiments performing, data interpretation, manuscript original drafting; VV, experiments performing; PV, ADV, resources work performing, sample collection; RR, MZ, study design, manuscript original drafting; VR, GV, CC, manuscript critical revision for important intellectual contribution. All authors read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work.  \nConflict of interest: the authors declare no competing interests and all authors confirm accuracy.  \nEthical approval: the experiments were approved by the Italian Ministry of Health on September 2nd, 2021 (protocol no. D9997.121) and performed according to the European Directive 86/609/EEC.  \nAvailability of data and materials: the datasets used and/or analyzed during the current study are available upon reasonable request from the corresponding author.  \nFunding: this study was supported by grants from the PRIN2022 (PRIN-MPN 2022) and Associazione Italiana Ricerca Cancro (AIRC IG23525) .  \n[European Journal of Histochemistry 2025; 69:4424]  \nIntroduction  \nThe bone marrow (BM) is a specialized microenvironment that supports hematopoiesis through two main anatomical and functional niches: the endosteal ","cbCaicaoHjgu2t90","https://ap.wps.com/l/cbCaicaoHjgu2t90","pdf",2971588,"English","# Introduction\n## Bone marrow niches and aging\n## Inflamm-aging and CHIP\n## Myelofibrosis as a model of niche disruption\n## Megakaryocytes as regulators of the HSC niche","[{\"question\":\"What role does the bone marrow niche play in hematopoietic stem cells?\",\"answer\":\"The bone marrow niche regulates HSC fate, and its integrity is essential for maintaining HSC function. Aging and rare diseases can significantly disrupt this niche.\"},{\"question\":\"How were HSC localization and dynamics assessed in this study?\",\"answer\":\"The study used huCD34tTA/TetO-H2BGFP reporter mice, analyzing HSC distribution in the bone marrow and quantifying nuclear GFP intensity to evaluate repopulating potential.\"},{\"question\":\"What changed in HSC-supportive megakaryocytes during myelofibrosis?\",\"answer\":\"In MF, the frequency of MKs with a supportive phenotype increased, but their ability to maintain HSCs in the niche was significantly impaired, contributing to altered HSC localization and mobilization.\"}]","The hematopoietic stem cells supportive megakaryocytes as shapers of the bone marrow niche - Original Article | PDF",1790730279,15]