Differential transcript usage unravels ...
Document type :
Compte-rendu et recension critique d'ouvrage
PMID :
Title :
Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains
Author(s) :
Marques-Coelho, Diego [Auteur]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Iohan, Lukas da Cruz Carvalho [Auteur]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Melo De Farias, Ana Raquel [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Flaig, Amandine [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Lambert, Jean-Charles [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Costa, Marcos Romualdo [Auteur correspondant]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Iohan, Lukas da Cruz Carvalho [Auteur]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Melo De Farias, Ana Raquel [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Flaig, Amandine [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Lambert, Jean-Charles [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Costa, Marcos Romualdo [Auteur correspondant]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Universidade Federal do Rio Grande do Norte [Natal] [UFRN]
Journal title :
npj Aging and Mechanisms of Disease
Pages :
2
Publisher :
Nature
Publication date :
2021
ISSN :
2056-3973
HAL domain(s) :
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]/Neurobiologie
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
English abstract : [en]
Alzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Yet, the pathophysiological processes involved in AD onset and progression are still poorly understood. Among numerous strategies, a comprehensive ...
Show more >Alzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Yet, the pathophysiological processes involved in AD onset and progression are still poorly understood. Among numerous strategies, a comprehensive overview of gene expression alterations in the diseased brain could contribute for a better understanding of the AD pathology. In this work, we probed the differential expression of genes in different brain regions of healthy and AD adult subjects using data from three large transcriptomic studies: Mayo Clinic, Mount Sinai Brain Bank (MSBB), and ROSMAP. Using a combination of differential expression of gene and isoform switch analyses, we provide a detailed landscape of gene expression alterations in the temporal and frontal lobes, harboring brain areas affected at early and late stages of the AD pathology, respectively. Next, we took advantage of an indirect approach to assign the complex gene expression changes revealed in bulk RNAseq to individual cell types/subtypes of the adult brain. This strategy allowed us to identify previously overlooked gene expression changes in the brain of AD patients. Among these alterations, we show isoform switches in the AD causal gene amyloid-beta precursor protein (APP) and the risk gene bridging integrator 1 (BIN1), which could have important functional consequences in neuronal cells. Altogether, our work proposes a novel integrative strategy to analyze RNAseq data in AD and other neurodegenerative diseases based on both gene/transcript expression and regional/cell-type specificities.Show less >
Show more >Alzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Yet, the pathophysiological processes involved in AD onset and progression are still poorly understood. Among numerous strategies, a comprehensive overview of gene expression alterations in the diseased brain could contribute for a better understanding of the AD pathology. In this work, we probed the differential expression of genes in different brain regions of healthy and AD adult subjects using data from three large transcriptomic studies: Mayo Clinic, Mount Sinai Brain Bank (MSBB), and ROSMAP. Using a combination of differential expression of gene and isoform switch analyses, we provide a detailed landscape of gene expression alterations in the temporal and frontal lobes, harboring brain areas affected at early and late stages of the AD pathology, respectively. Next, we took advantage of an indirect approach to assign the complex gene expression changes revealed in bulk RNAseq to individual cell types/subtypes of the adult brain. This strategy allowed us to identify previously overlooked gene expression changes in the brain of AD patients. Among these alterations, we show isoform switches in the AD causal gene amyloid-beta precursor protein (APP) and the risk gene bridging integrator 1 (BIN1), which could have important functional consequences in neuronal cells. Altogether, our work proposes a novel integrative strategy to analyze RNAseq data in AD and other neurodegenerative diseases based on both gene/transcript expression and regional/cell-type specificities.Show less >
Language :
Anglais
Popular science :
Non
Collections :
Source :
Files
- document
- Open access
- Access the document
- s41514-020-00052-5.pdf
- Open access
- Access the document