Shared Blood Transcriptomic Signatures between Alzheimer’s Disease and Diabetes Mellitus

Lee, Taesic; Lee, Hyunju

doi:10.3390/biomedicines9010034

Cited by 21 publications

(26 citation statements)

References 59 publications

(60 reference statements)

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“…At present, there are no reports about these two TFs and PE. GTF2B is one of the ubiquitous TFs required for transcription initiation, and it has been reported to be closely related to Alzheimer’s disease and type 2 diabetes ( Lee and Lee, 2021 ). The CCAAT/enhancer binding protein CEBPB belongs to a family of leucine-zipper TFs that participate in physiological processes such as energy metabolism, cell proliferation, and differentiation ( Huang et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing

Zhou

Wang

Yang

et al. 2022

Molecules and Cells

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Trophoblasts, important functional cells in the placenta, play a critical role in maintaining placental function. The heterogeneity of trophoblasts has been reported, but little is known about the trophoblast subtypes and distinctive functions during preeclampsia (PE). In this study, we aimed to gain insight into the cell type-specific transcriptomic changes by performing unbiased single-cell RNA sequencing (scRNA-seq) of placental tissue samples, including those of patients diagnosed with PE and matched healthy controls. A total of 29,006 cells were identified in 11 cell types, including trophoblasts and immune cells, and the functions of the trophoblast subtypes in the PE group and the control group were also analyzed. As an important trophoblast subtype, extravillous trophoblasts (EVTs) were further divided into 4 subgroups, and their functions were preliminarily analyzed. We found that some biological processes related to pregnancy, hormone secretion and immunity changed in the PE group. We also identified and analyzed the regulatory network of transcription factors (TFs) identified in the EVTs, among which 3 modules were decreased in the PE group. Then, through in vitro cell experiments, we found that in one of the modules, CEBPB and GTF2B may be involved in EVT dysfunction in PE. In conclusion, our study showed the different transcriptional profiles and regulatory modules in trophoblasts between placentas in the control and PE groups at the single-cell level; these changes may be involved in the pathological process of PE, providing a new molecular theoretical basis for preeclamptic trophoblast dysfunction.

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Section: Resultsmentioning

confidence: 99%

Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing

Zhou

Wang

Yang

et al. 2022

Molecules and Cells

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“…A previous study [ 23 ] suggested that analyzing numerous gene expression datasets could cause a considerable amount of transcript information (due to the different platforms used for measuring gene expression) and trait-related signature data (due to the different phenotypical or disease statuses among the individual datasets) loss. Therefore, a MetaQC method that provides a score for the quality of the gene expression datasets for the meta-analysis [ 24 ] was used to enable the selection of high-quality blood gene expression datasets, which were then used for feature selection.…”

Section: Methodsmentioning

confidence: 99%

“…A previous study used the TFs obtained from TRANSFACT [ 33 ] to predict blood AD cases among the different cohorts [ 30 ]. In addition, the updated TF catalog by Lambert et al [ 34 ] was used to identify the shared upstream blood genes between AD and diabetes [ 23 ]. Based on these studies, we implemented the TF list that had been manually updated by Lambert et al [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Disease-Related Genes That Are Common between Alzheimer’s and Cardiovascular Disease Using Blood Genome-Wide Transcriptome Analysis

Lee

2021

Biomedicines

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Accumulating evidence has suggested a shared pathophysiology between Alzheimer’s disease (AD) and cardiovascular disease (CVD). Based on genome-wide transcriptomes, specifically those of blood samples, we identify the shared disease-related signatures between AD and CVD. In addition to gene expressions in blood, the following prior knowledge were utilized to identify several candidate disease-related gene (DRG) sets: protein–protein interactions, transcription factors, disease–gene relationship databases, and single nucleotide polymorphisms. We selected the respective DRG sets for AD and CVD that show a high accuracy for disease prediction in bulk and single-cell gene expression datasets. Then, gene regulatory networks (GRNs) were constructed from each of the AD and CVD DRG sets to identify the upstream regulating genes. Using the GRNs, we identified two common upstream genes (GPBP1 and SETDB2) between the AD and CVD GRNs. In summary, this study has identified the potential AD- and CVD-related genes and common hub genes between these sets, which may help to elucidate the shared mechanisms between these two diseases.

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“…Mitochondrial dysfunction is involved in the onset and progression of neurodegenerative diseases [ 61 , 62 , 63 , 64 ]. It is therefore likely that the beneficial effects of BFT administration on mitochondrial function is not restricted to the activation of the ThDP-dependent enzyme complexes PDHC and OGDHC.…”

Section: Properties and Mechanism Of Action Of Benfotiaminementioning

confidence: 99%

Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine

Sambon

Wins

Bettendorff

2021

IJMS

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Thiamine (vitamin B1) is essential for brain function because of the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. In order to compensate thiamine deficiency, several thiamine precursors with higher bioavailability were developed since the 1950s. Among these, the thioester benfotiamine (BFT) has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. BFT has no adverse effects and improves cognitive outcome in patients with mild Alzheimer’s disease (AD). Recent in vitro studies show that another thiamine thioester, dibenzoylthiamine (DBT) is even more efficient that BFT, especially with respect to its anti-inflammatory potency. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified metabolites in particular open thiazole ring derivatives. The identification of the active neuroprotective derivatives and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental and psychiatric conditions.

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Shared Blood Transcriptomic Signatures between Alzheimer’s Disease and Diabetes Mellitus

Cited by 21 publications

References 59 publications

Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing

Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing

Identification of Disease-Related Genes That Are Common between Alzheimer’s and Cardiovascular Disease Using Blood Genome-Wide Transcriptome Analysis

Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine

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