Transcriptomic profiling of platelet senescence and platelet extracellular vesicles

Autores
Pienimaeki Roemer, Annika; Konovalova, Tatiana; Musri, Melina Mara; Sigruener, Alexander; Boettcher, Alfred; Meister, Gunter; Schmitz, Gerd
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Platelets (PLTs) are derived from megakaryocytes during PLT shedding. Senescent or activated PLTs are expanded in vascular and neurological diseases and release PLT extracellular vesicles (PL-EVs). A systematic analysis of regular messenger RNA (mRNA) and small RNA composition in PLTs and PL-EVs during in vitro PLT senescence has not yet been published. STUDY DESIGN AND METHODS: We isolated PLTs, total PL-EVs, and PL-EV subsets on Days 0 and 5 from human stored donor platelet concentrates. Isolated mRNA species and microRNA (miRNA) species were analyzed by microarrays and deep sequencing. Correlation of mRNA and miRNA species (miR) and miRNA target analyses were performed using bioinformatics. RESULTS: During in vitro PLT senescence, residual PLT mRNA species were decreased and partially converted to miRNA species. Residual mRNAs included encoded genes relevant for atherosclerosis, inflammation (matrix metallopeptidase 14 [MMP-14], granulin [GRN], angiopoietin like 2 [ANGPTL2]), and neurotransmission (dopamine receptor 2 [DRD2], γ-aminobutyric acid type A receptor ρ3 [GABRR3]). Compared with senescent PLTs, PL-EVs have up-regulated their miRNA species involved in “diabesity” and in vascular and metabolic disease (miR-144-3p, miR-486-5p, miR-142-5p, miR-451a, miR-25-3p, miR-145-5p, and let-7f-5p). The 100 highest expressed PL-EV miRNA species determined by microarrays were compared with the 100 highest expressed PL-EV miRNA species detected by deep sequencing. This approach resulted in 66 overlaps. The regulated miRNAs (assessed by both methods) were related to neurological disorders, including targets for Alzheimer's disease (e.g., β-site amyloid precursor protein APP-cleaving enzyme 1 [BACE1], translocase of outer mitochondrial membrane 40 homolog [TOMM40], neuron navigator 3 [NAV3]). CONCLUSION: During in vitro senescence, PLTs degrade large RNA species. Concomitantly, they up-regulate a distinct set of known small RNA species involved in atherosclerosis, inflammation, and neurodegeneration. PL-EVs enrich miRNA species, likely supporting the role of PLTs and PL-EVs in vascular homeostasis and as carriers of neurodegenerative disease-related miRNA cargo.
Fil: Pienimaeki Roemer, Annika. Universitat Regensburg; Alemania
Fil: Konovalova, Tatiana. Universitat Regensburg; Alemania
Fil: Musri, Melina Mara. Universitat Regensburg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Sigruener, Alexander. Universitat Regensburg; Alemania
Fil: Boettcher, Alfred. Universitat Regensburg; Alemania
Fil: Meister, Gunter. Universitat Regensburg; Alemania
Fil: Schmitz, Gerd. Universitat Regensburg; Alemania
Materia
Platelets
Extracellular Vesicles
Micrornas
Transcriptomic Profiling
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/74837
Acceder
id CONICETDig_2e134b931958aed2753c8857ef5a038b
oai_identifier_str oai:ri.conicet.gov.ar:11336/74837
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transcriptomic profiling of platelet senescence and platelet extracellular vesiclesPienimaeki Roemer, AnnikaKonovalova, TatianaMusri, Melina MaraSigruener, AlexanderBoettcher, AlfredMeister, GunterSchmitz, GerdPlateletsExtracellular VesiclesMicrornasTranscriptomic Profilinghttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND: Platelets (PLTs) are derived from megakaryocytes during PLT shedding. Senescent or activated PLTs are expanded in vascular and neurological diseases and release PLT extracellular vesicles (PL-EVs). A systematic analysis of regular messenger RNA (mRNA) and small RNA composition in PLTs and PL-EVs during in vitro PLT senescence has not yet been published. STUDY DESIGN AND METHODS: We isolated PLTs, total PL-EVs, and PL-EV subsets on Days 0 and 5 from human stored donor platelet concentrates. Isolated mRNA species and microRNA (miRNA) species were analyzed by microarrays and deep sequencing. Correlation of mRNA and miRNA species (miR) and miRNA target analyses were performed using bioinformatics. RESULTS: During in vitro PLT senescence, residual PLT mRNA species were decreased and partially converted to miRNA species. Residual mRNAs included encoded genes relevant for atherosclerosis, inflammation (matrix metallopeptidase 14 [MMP-14], granulin [GRN], angiopoietin like 2 [ANGPTL2]), and neurotransmission (dopamine receptor 2 [DRD2], γ-aminobutyric acid type A receptor ρ3 [GABRR3]). Compared with senescent PLTs, PL-EVs have up-regulated their miRNA species involved in “diabesity” and in vascular and metabolic disease (miR-144-3p, miR-486-5p, miR-142-5p, miR-451a, miR-25-3p, miR-145-5p, and let-7f-5p). The 100 highest expressed PL-EV miRNA species determined by microarrays were compared with the 100 highest expressed PL-EV miRNA species detected by deep sequencing. This approach resulted in 66 overlaps. The regulated miRNAs (assessed by both methods) were related to neurological disorders, including targets for Alzheimer's disease (e.g., β-site amyloid precursor protein APP-cleaving enzyme 1 [BACE1], translocase of outer mitochondrial membrane 40 homolog [TOMM40], neuron navigator 3 [NAV3]). CONCLUSION: During in vitro senescence, PLTs degrade large RNA species. Concomitantly, they up-regulate a distinct set of known small RNA species involved in atherosclerosis, inflammation, and neurodegeneration. PL-EVs enrich miRNA species, likely supporting the role of PLTs and PL-EVs in vascular homeostasis and as carriers of neurodegenerative disease-related miRNA cargo.Fil: Pienimaeki Roemer, Annika. Universitat Regensburg; AlemaniaFil: Konovalova, Tatiana. Universitat Regensburg; AlemaniaFil: Musri, Melina Mara. Universitat Regensburg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Sigruener, Alexander. Universitat Regensburg; AlemaniaFil: Boettcher, Alfred. Universitat Regensburg; AlemaniaFil: Meister, Gunter. Universitat Regensburg; AlemaniaFil: Schmitz, Gerd. Universitat Regensburg; AlemaniaWiley Blackwell Publishing, Inc2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/74837Pienimaeki Roemer, Annika; Konovalova, Tatiana; Musri, Melina Mara; Sigruener, Alexander; Boettcher, Alfred; et al.; Transcriptomic profiling of platelet senescence and platelet extracellular vesicles; Wiley Blackwell Publishing, Inc; Transfusion; 57; 1; 1-2017; 144-1560041-1132CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/trf.13896info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/trf.13896info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:08Zoai:ri.conicet.gov.ar:11336/74837instacron: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 09:44:09.1CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
title Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
spellingShingle Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
Pienimaeki Roemer, Annika
Platelets
Extracellular Vesicles
Micrornas
Transcriptomic Profiling
title_short Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
title_full Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
title_fullStr Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
title_full_unstemmed Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
title_sort Transcriptomic profiling of platelet senescence and platelet extracellular vesicles
dc.creator.none.fl_str_mv Pienimaeki Roemer, Annika
Konovalova, Tatiana
Musri, Melina Mara
Sigruener, Alexander
Boettcher, Alfred
Meister, Gunter
Schmitz, Gerd
author Pienimaeki Roemer, Annika
author_facet Pienimaeki Roemer, Annika
Konovalova, Tatiana
Musri, Melina Mara
Sigruener, Alexander
Boettcher, Alfred
Meister, Gunter
Schmitz, Gerd
author_role author
author2 Konovalova, Tatiana
Musri, Melina Mara
Sigruener, Alexander
Boettcher, Alfred
Meister, Gunter
Schmitz, Gerd
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Platelets
Extracellular Vesicles
Micrornas
Transcriptomic Profiling
topic Platelets
Extracellular Vesicles
Micrornas
Transcriptomic Profiling
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: Platelets (PLTs) are derived from megakaryocytes during PLT shedding. Senescent or activated PLTs are expanded in vascular and neurological diseases and release PLT extracellular vesicles (PL-EVs). A systematic analysis of regular messenger RNA (mRNA) and small RNA composition in PLTs and PL-EVs during in vitro PLT senescence has not yet been published. STUDY DESIGN AND METHODS: We isolated PLTs, total PL-EVs, and PL-EV subsets on Days 0 and 5 from human stored donor platelet concentrates. Isolated mRNA species and microRNA (miRNA) species were analyzed by microarrays and deep sequencing. Correlation of mRNA and miRNA species (miR) and miRNA target analyses were performed using bioinformatics. RESULTS: During in vitro PLT senescence, residual PLT mRNA species were decreased and partially converted to miRNA species. Residual mRNAs included encoded genes relevant for atherosclerosis, inflammation (matrix metallopeptidase 14 [MMP-14], granulin [GRN], angiopoietin like 2 [ANGPTL2]), and neurotransmission (dopamine receptor 2 [DRD2], γ-aminobutyric acid type A receptor ρ3 [GABRR3]). Compared with senescent PLTs, PL-EVs have up-regulated their miRNA species involved in “diabesity” and in vascular and metabolic disease (miR-144-3p, miR-486-5p, miR-142-5p, miR-451a, miR-25-3p, miR-145-5p, and let-7f-5p). The 100 highest expressed PL-EV miRNA species determined by microarrays were compared with the 100 highest expressed PL-EV miRNA species detected by deep sequencing. This approach resulted in 66 overlaps. The regulated miRNAs (assessed by both methods) were related to neurological disorders, including targets for Alzheimer's disease (e.g., β-site amyloid precursor protein APP-cleaving enzyme 1 [BACE1], translocase of outer mitochondrial membrane 40 homolog [TOMM40], neuron navigator 3 [NAV3]). CONCLUSION: During in vitro senescence, PLTs degrade large RNA species. Concomitantly, they up-regulate a distinct set of known small RNA species involved in atherosclerosis, inflammation, and neurodegeneration. PL-EVs enrich miRNA species, likely supporting the role of PLTs and PL-EVs in vascular homeostasis and as carriers of neurodegenerative disease-related miRNA cargo.
Fil: Pienimaeki Roemer, Annika. Universitat Regensburg; Alemania
Fil: Konovalova, Tatiana. Universitat Regensburg; Alemania
Fil: Musri, Melina Mara. Universitat Regensburg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Sigruener, Alexander. Universitat Regensburg; Alemania
Fil: Boettcher, Alfred. Universitat Regensburg; Alemania
Fil: Meister, Gunter. Universitat Regensburg; Alemania
Fil: Schmitz, Gerd. Universitat Regensburg; Alemania
description BACKGROUND: Platelets (PLTs) are derived from megakaryocytes during PLT shedding. Senescent or activated PLTs are expanded in vascular and neurological diseases and release PLT extracellular vesicles (PL-EVs). A systematic analysis of regular messenger RNA (mRNA) and small RNA composition in PLTs and PL-EVs during in vitro PLT senescence has not yet been published. STUDY DESIGN AND METHODS: We isolated PLTs, total PL-EVs, and PL-EV subsets on Days 0 and 5 from human stored donor platelet concentrates. Isolated mRNA species and microRNA (miRNA) species were analyzed by microarrays and deep sequencing. Correlation of mRNA and miRNA species (miR) and miRNA target analyses were performed using bioinformatics. RESULTS: During in vitro PLT senescence, residual PLT mRNA species were decreased and partially converted to miRNA species. Residual mRNAs included encoded genes relevant for atherosclerosis, inflammation (matrix metallopeptidase 14 [MMP-14], granulin [GRN], angiopoietin like 2 [ANGPTL2]), and neurotransmission (dopamine receptor 2 [DRD2], γ-aminobutyric acid type A receptor ρ3 [GABRR3]). Compared with senescent PLTs, PL-EVs have up-regulated their miRNA species involved in “diabesity” and in vascular and metabolic disease (miR-144-3p, miR-486-5p, miR-142-5p, miR-451a, miR-25-3p, miR-145-5p, and let-7f-5p). The 100 highest expressed PL-EV miRNA species determined by microarrays were compared with the 100 highest expressed PL-EV miRNA species detected by deep sequencing. This approach resulted in 66 overlaps. The regulated miRNAs (assessed by both methods) were related to neurological disorders, including targets for Alzheimer's disease (e.g., β-site amyloid precursor protein APP-cleaving enzyme 1 [BACE1], translocase of outer mitochondrial membrane 40 homolog [TOMM40], neuron navigator 3 [NAV3]). CONCLUSION: During in vitro senescence, PLTs degrade large RNA species. Concomitantly, they up-regulate a distinct set of known small RNA species involved in atherosclerosis, inflammation, and neurodegeneration. PL-EVs enrich miRNA species, likely supporting the role of PLTs and PL-EVs in vascular homeostasis and as carriers of neurodegenerative disease-related miRNA cargo.
publishDate 2017
dc.date.none.fl_str_mv 2017-01
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/11336/74837
Pienimaeki Roemer, Annika; Konovalova, Tatiana; Musri, Melina Mara; Sigruener, Alexander; Boettcher, Alfred; et al.; Transcriptomic profiling of platelet senescence and platelet extracellular vesicles; Wiley Blackwell Publishing, Inc; Transfusion; 57; 1; 1-2017; 144-156
0041-1132
CONICET Digital
CONICET
url http://hdl.handle.net/11336/74837
identifier_str_mv Pienimaeki Roemer, Annika; Konovalova, Tatiana; Musri, Melina Mara; Sigruener, Alexander; Boettcher, Alfred; et al.; Transcriptomic profiling of platelet senescence and platelet extracellular vesicles; Wiley Blackwell Publishing, Inc; Transfusion; 57; 1; 1-2017; 144-156
0041-1132
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/trf.13896
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/trf.13896
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
_version_ 1842268648053407744
score 13.13397

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