Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Nat Commun ; 14(1): 3280, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286573

RESUMO

Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.


Assuntos
Tromboembolia Venosa , Humanos , Biomarcadores , Ativação do Complemento , Fator H do Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Fator V , Tromboembolia Venosa/genética
2.
Cell Rep ; 40(2): 111046, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35830816

RESUMO

The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed primarily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell RNA sequencing (scRNA-seq) datasets, despite being the primary functional cell type. Here, we decipher cell-type-enriched transcriptomes from unfractionated human adipose tissue RNA-seq data. We profile all major constituent cell types, using 527 visceral adipose tissue (VAT) or 646 subcutaneous adipose tissue (SAT) samples, identifying over 2,300 cell-type-enriched transcripts. Sex-subset analysis uncovers a panel of male-only cell-type-enriched genes. By resolving expression profiles of genes differentially expressed between SAT and VAT, we identify mesothelial cells as the primary driver of this variation. This study provides an accessible method to profile cell-type-enriched transcriptomes using bulk RNA-seq, generating a roadmap for adipose tissue biology.


Assuntos
Gordura Subcutânea , Transcriptoma , Tecido Adiposo/metabolismo , Perfilação da Expressão Gênica , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Gordura Subcutânea/metabolismo , Transcriptoma/genética
3.
Cell Rep ; 29(6): 1690-1706.e4, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31693905

RESUMO

Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic, and malignant disorders. The importance of defining cell-type-specific genes and their modification in disease is increasingly recognized. Here, we develop a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNA sequencing (RNA-seq) data from 238 normal human cortex samples from 2 independent cohorts. We compare endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte, neuron, and microglial cell profiles. Endothelial changes in malignant disease are explored using RNA-seq data from 516 lower-grade gliomas and 401 glioblastomas. Lower-grade gliomas appear to be an "endothelial intermediate" between normal brain and glioblastoma. We apply our method for the prediction of glioblastoma-specific endothelial biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain, using a method developed to resolve bulk RNA-seq into constituent cell-type-enriched profiles.


Assuntos
Astrócitos/metabolismo , Neoplasias Encefálicas/metabolismo , Endotélio Vascular/metabolismo , Glioblastoma/metabolismo , Glioma/metabolismo , Neurônios/metabolismo , Oligodendroglia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrócitos/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Córtex Cerebelar/metabolismo , Córtex Cerebelar/patologia , Estudos de Coortes , Biologia Computacional , Bases de Dados Genéticas , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Oligodendroglia/patologia , Proteoma/metabolismo , RNA-Seq , Análise de Célula Única , Transcriptoma
5.
Cell Syst ; 3(3): 287-301.e3, 2016 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-27641958

RESUMO

Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds. The majority of identified transcripts could be detected in cultured endothelial cells from various vascular beds, and we observed maintenance of relative expression in early passage cells. In summary, we describe a widely applicable method to determine cell-type-specific transcriptome profiles in a whole-organism context, based on differential abundance across tissues. We identify potential vascular drug targets or endothelial biomarkers and highlight candidates for functional studies to increase understanding of the endothelium in health and disease.


Assuntos
Transcriptoma , Biomarcadores , Células Cultivadas , Células Endoteliais , Endotélio Vascular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA