Dataset Information

Combinatorial analyses reveal cellular composition changes have different impacts on transcriptomic changes of cell type specific genes in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) brains are characterized by progressive neuron loss and gliosis. Previous studies of gene expression using bulk tissue samples often fail to consider changes in cell-type composition when comparing AD versus control, which can lead to differences in expression levels that are not due to transcriptional regulation. We mined five large transcriptomic AD datasets for conserved gene co-expression module, then analyzed differential expression and differential co-expression within the modules between AD samples and controls. We performed cell-type deconvolution analysis to determine whether the observed differential expression was due to changes in cell-type proportions in the samples or to transcriptional regulation. Our findings were validated using four additional datasets. We discovered that the increased expression of microglia modules in the AD samples can be explained by increased microglia proportions in the AD samples. In contrast, decreased expression and perturbed co-expression within neuron modules in the AD samples was likely due in part to altered regulation of neuronal pathways. Several transcription factors that are differentially expressed in AD might account for such altered gene regulation. Similarly, changes in gene expression and co-expression within astrocyte modules could be attributed to combined effects of astrogliosis and astrocyte gene activation. Gene expression in the astrocyte modules was also strongly correlated with clinicopathological biomarkers. Through this work, we demonstrated that combinatorial analysis can delineate the origins of transcriptomic changes in bulk tissue data and shed light on key genes and pathways involved in AD.

SUBMITTER: Johnson TS

PROVIDER: S-EPMC7801680 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Combinatorial analyses reveal cellular composition changes have different impacts on transcriptomic changes of cell type specific genes in Alzheimer's Disease.

Johnson Travis S TS Xiang Shunian S Dong Tianhan T Huang Zhi Z Cheng Michael M Wang Tianfu T Yang Kai K Ni Dong D Huang Kun K Zhang Jie J

Scientific reports 20210111 1

Alzheimer's disease (AD) brains are characterized by progressive neuron loss and gliosis. Previous studies of gene expression using bulk tissue samples often fail to consider changes in cell-type composition when comparing AD versus control, which can lead to differences in expression levels that are not due to transcriptional regulation. We mined five large transcriptomic AD datasets for conserved gene co-expression module, then analyzed differential expression and differential co-expression wi ...[more]

PMID: 33432017

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Project description:BACKGROUND:Citrus blight is a very important progressive decline disease of commercial citrus. The etiology is unknown, although the disease can be transmitted by root grafts, suggesting a viral etiology. Diagnosis is made by demonstrating physical blockage of xylem cells that prevents the movement of water. This test was used to identify symptomatic trees from four commercial groves in Florida. Total RNA extracts of phloem-enriched scaffold root tissues were prepared from seven trees that failed to take up water and from one healthy tree. These RNA extracts were used for transcriptomic analyses using paired end RNA-Seq from an Illumina 2500 system. The expression of transcripts annotated as polyprotein of citrus endogenous pararetrovirus were estimated by both RT-qPCR and RNA-Seq. RESULTS:Transcripts from seven RNA-Seq libraries from trees affected by citrus blight were compared to a control tree. 129-148 million RNA fragments (two paired-end reads/fragment) were generated per library and were mapped to the sweet orange reference genome. In response to citrus blight stress, genes encoding aquaporins, proteins with water channel activity and several cellulose synthase genes were down-regulated, whereas genes involved in lignin and glucosinolate biosynthesis were up-regulated. Transcripts encoding proteins in pathways of carbohydrate metabolism, nucleotide synthesis, signaling, hormone metabolism, secondary metabolism, transport, and biotic stress pathways were overwhelmingly down regulated in all libraries. CONCLUSION:Reduced water intake and xylem plugging were observed in the trees tested and the changes in their transcriptome were analyzed. Plants adapted to reduced water flow by regulating primary and secondary metabolism, nuclear transport and hormone associated pathways. The patterns of energy generation, transcription, translation and protein degradation were consistent with irreversible decline. The down regulation of cellulose synthase transcripts and up regulation of transcripts related to lignin production likely lead to an imbalance in the pathways leading to wood formation, and may lead to the blockage of the xylem vessels seen as the cardinal symptom of citrus blight. Transcripts of a pararetrovirus were elevated in the transcriptome of roots used in this study.

Dataset Information

Combinatorial analyses reveal cellular composition changes have different impacts on transcriptomic changes of cell type specific genes in Alzheimer's Disease.

Publications

Combinatorial analyses reveal cellular composition changes have different impacts on transcriptomic changes of cell type specific genes in Alzheimer's Disease.

Similar Datasets

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