Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients

Autores
Di Buduo, Christian A.; Alberelli, Maria Adele; Glembotsky, Ana Claudia; Podda, Gianmarco; Lev, Paola Roxana; Cattaneo, Marco; Landolfi, Raffaele; Heller, Paula Graciela; Balduini, Alessandra; De Candia, Erica
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by deficiency ofplatelet α-granules, macrothrombocytopenia and marrow fibrosis. The autosomal recessive form ofGPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule traffickingin megakaryocytes, the platelet progenitors. We report the first analysis of cultured megakaryocytesfrom GPS patients with NBEAL2 mutations. Megakaryocytes cultured from peripheral blood or bonemarrow hematopoietic progenitor cells from four patients were used to investigate megakaryopoiesis,megakaryocyte morphology and platelet formation. In vitro differentiation of megakaryocytes wasnormal, whereas we observed deficiency of megakaryocyte α-granule proteins and emperipolesis.Importantly, we first demonstrated that platelet formation by GPS megakaryocytes was severelyaffected, a defect which might be the major cause of thrombocytopenia in patients. These resultsdemonstrate that cultured megakaryocytes from GPS patients provide a valuable model to understandthe pathogenesis of GPS in humans.
Fil: Di Buduo, Christian A.. Università degli studi di Pavia; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo; Italia
Fil: Alberelli, Maria Adele. Università Cattolica del Sacro Cuore; Italia
Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Podda, Gianmarco. Università degli Studi di Milano; Italia
Fil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia
Fil: Landolfi, Raffaele. Università Cattolica del Sacro Cuore; Italia
Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Balduini, Alessandra. Università degli studi di Pavia; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo; Italia. Tufts University; Estados Unidos
Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia
Materia
Gray Platelet
Nbeal2
Thrombopoiesis
Megakaryocyte
Haematological Diseases
Medical Research
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/44591
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/44591
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patientsDi Buduo, Christian A.Alberelli, Maria AdeleGlembotsky, Ana ClaudiaPodda, GianmarcoLev, Paola RoxanaCattaneo, MarcoLandolfi, RaffaeleHeller, Paula GracielaBalduini, AlessandraDe Candia, EricaGray PlateletNbeal2ThrombopoiesisMegakaryocyteHaematological DiseasesMedical Researchhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by deficiency ofplatelet α-granules, macrothrombocytopenia and marrow fibrosis. The autosomal recessive form ofGPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule traffickingin megakaryocytes, the platelet progenitors. We report the first analysis of cultured megakaryocytesfrom GPS patients with NBEAL2 mutations. Megakaryocytes cultured from peripheral blood or bonemarrow hematopoietic progenitor cells from four patients were used to investigate megakaryopoiesis,megakaryocyte morphology and platelet formation. In vitro differentiation of megakaryocytes wasnormal, whereas we observed deficiency of megakaryocyte α-granule proteins and emperipolesis.Importantly, we first demonstrated that platelet formation by GPS megakaryocytes was severelyaffected, a defect which might be the major cause of thrombocytopenia in patients. These resultsdemonstrate that cultured megakaryocytes from GPS patients provide a valuable model to understandthe pathogenesis of GPS in humans.Fil: Di Buduo, Christian A.. Università degli studi di Pavia; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo; ItaliaFil: Alberelli, Maria Adele. Università Cattolica del Sacro Cuore; ItaliaFil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Podda, Gianmarco. Università degli Studi di Milano; ItaliaFil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cattaneo, Marco. Università degli Studi di Milano; ItaliaFil: Landolfi, Raffaele. Università Cattolica del Sacro Cuore; ItaliaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Balduini, Alessandra. Università degli studi di Pavia; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo; Italia. Tufts University; Estados UnidosFil: De Candia, Erica. Università Cattolica del Sacro Cuore; ItaliaNature Publishing Group2016-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/44591Di Buduo, Christian A.; Alberelli, Maria Adele; Glembotsky, Ana Claudia; Podda, Gianmarco; Lev, Paola Roxana; et al.; Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients; Nature Publishing Group; Scientific Reports; 6; 3-2016; 1-10; 232132045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep23213info:eu-repo/semantics/altIdentifier/doi/10.1038/srep23213info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:40Zoai:ri.conicet.gov.ar:11336/44591instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:00:40.78CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
title Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
spellingShingle Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
Di Buduo, Christian A.
Gray Platelet
Nbeal2
Thrombopoiesis
Megakaryocyte
Haematological Diseases
Medical Research
title_short Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
title_full Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
title_fullStr Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
title_full_unstemmed Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
title_sort Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients
dc.creator.none.fl_str_mv Di Buduo, Christian A.
Alberelli, Maria Adele
Glembotsky, Ana Claudia
Podda, Gianmarco
Lev, Paola Roxana
Cattaneo, Marco
Landolfi, Raffaele
Heller, Paula Graciela
Balduini, Alessandra
De Candia, Erica
author Di Buduo, Christian A.
author_facet Di Buduo, Christian A.
Alberelli, Maria Adele
Glembotsky, Ana Claudia
Podda, Gianmarco
Lev, Paola Roxana
Cattaneo, Marco
Landolfi, Raffaele
Heller, Paula Graciela
Balduini, Alessandra
De Candia, Erica
author_role author
author2 Alberelli, Maria Adele
Glembotsky, Ana Claudia
Podda, Gianmarco
Lev, Paola Roxana
Cattaneo, Marco
Landolfi, Raffaele
Heller, Paula Graciela
Balduini, Alessandra
De Candia, Erica
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Gray Platelet
Nbeal2
Thrombopoiesis
Megakaryocyte
Haematological Diseases
Medical Research
topic Gray Platelet
Nbeal2
Thrombopoiesis
Megakaryocyte
Haematological Diseases
Medical Research
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by deficiency ofplatelet α-granules, macrothrombocytopenia and marrow fibrosis. The autosomal recessive form ofGPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule traffickingin megakaryocytes, the platelet progenitors. We report the first analysis of cultured megakaryocytesfrom GPS patients with NBEAL2 mutations. Megakaryocytes cultured from peripheral blood or bonemarrow hematopoietic progenitor cells from four patients were used to investigate megakaryopoiesis,megakaryocyte morphology and platelet formation. In vitro differentiation of megakaryocytes wasnormal, whereas we observed deficiency of megakaryocyte α-granule proteins and emperipolesis.Importantly, we first demonstrated that platelet formation by GPS megakaryocytes was severelyaffected, a defect which might be the major cause of thrombocytopenia in patients. These resultsdemonstrate that cultured megakaryocytes from GPS patients provide a valuable model to understandthe pathogenesis of GPS in humans.
Fil: Di Buduo, Christian A.. Università degli studi di Pavia; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo; Italia
Fil: Alberelli, Maria Adele. Università Cattolica del Sacro Cuore; Italia
Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Podda, Gianmarco. Università degli Studi di Milano; Italia
Fil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia
Fil: Landolfi, Raffaele. Università Cattolica del Sacro Cuore; Italia
Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Balduini, Alessandra. Università degli studi di Pavia; Italia. Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo; Italia. Tufts University; Estados Unidos
Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia
description The Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by deficiency ofplatelet α-granules, macrothrombocytopenia and marrow fibrosis. The autosomal recessive form ofGPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule traffickingin megakaryocytes, the platelet progenitors. We report the first analysis of cultured megakaryocytesfrom GPS patients with NBEAL2 mutations. Megakaryocytes cultured from peripheral blood or bonemarrow hematopoietic progenitor cells from four patients were used to investigate megakaryopoiesis,megakaryocyte morphology and platelet formation. In vitro differentiation of megakaryocytes wasnormal, whereas we observed deficiency of megakaryocyte α-granule proteins and emperipolesis.Importantly, we first demonstrated that platelet formation by GPS megakaryocytes was severelyaffected, a defect which might be the major cause of thrombocytopenia in patients. These resultsdemonstrate that cultured megakaryocytes from GPS patients provide a valuable model to understandthe pathogenesis of GPS in humans.
publishDate 2016
dc.date.none.fl_str_mv 2016-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/44591
Di Buduo, Christian A.; Alberelli, Maria Adele; Glembotsky, Ana Claudia; Podda, Gianmarco; Lev, Paola Roxana; et al.; Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients; Nature Publishing Group; Scientific Reports; 6; 3-2016; 1-10; 23213
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/44591
identifier_str_mv Di Buduo, Christian A.; Alberelli, Maria Adele; Glembotsky, Ana Claudia; Podda, Gianmarco; Lev, Paola Roxana; et al.; Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients; Nature Publishing Group; Scientific Reports; 6; 3-2016; 1-10; 23213
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep23213
info:eu-repo/semantics/altIdentifier/doi/10.1038/srep23213
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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