Uncovering the role of G9a modulatory landscape promoting neuronal plasticity and neuroprotection in Alzheimer's disease

Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we uncover the unknown G9a modulation pathways involved in AD, showing the upregulation of G9a and H3K9me2 in the brains of AD patients. Likewise, treatment with a G9a inhibitor in SAMP8 mice reversed the high levels of H3K9me2 and rescued the cognitive decline. Interestingly, a transcriptional profile analysis revealed induction of neuronal plasticity and a reduction of oxidative stress and neuroinflammation; the latter being also validated in cell cultures. Furthermore, an exploratory H3K9me2 ChIP-seq analysis demonstrated that during G9a inhibition treatment, the H3K9me2 mark is enriched at the promoter of genes associated with neural functions. Lastly, we showed in Caenorhabditis elegans (C. elegans) AD transgenic strains, similar epigenetic modifications and modulated pathways were altered with increased β-amyloid levels, which were reverted by the set-25 (in C. elegans is similar to the mammalian G9a protein) knockout, including the cognitive impairment. Therefore, our findings confirm that RNAi suppression of set-25 or pharmacological G9a inhibition promotes a positive outcome in AD, being a promising therapeutic strategy.

Advances in single-cell sequencing: insights from organ transplantation

Single-cell RNA sequencing (scRNA-seq) is a comprehensive technical tool to analyze intracellular and intercellular interaction data by whole transcriptional profile analysis. Here, we describe the application in biomedical research, focusing on the immune system during organ transplantation and rejection. Unlike conventional transcriptome analysis, this method provides a full map of multiple cell populations in one specific tissue and presents a dynamic and transient unbiased method to explore the progression of allograft dysfunction, starting from the stress response to final graft failure. This promising sequencing technology remarkably improves individualized organ rejection treatment by identifying decisive cellular subgroups and cell-specific interactions.

Enriching Genomic Resources and Transcriptional Profile Analysis of Miscanthus sinensis under Drought Stress Based on RNA Sequencing

Miscanthus × giganteus is wildly cultivated as a potential biofuel feedstock around the world; however, the narrow genetic basis and sterile characteristics have become a limitation for its utilization. As a progenitor of M. × giganteus, M. sinensis is widely distributed around East Asia providing well abiotic stress tolerance. To enrich the M. sinensis genomic databases and resources, we sequenced and annotated the transcriptome of M. sinensis by using an Illumina HiSeq 2000 platform. Approximately 316 million high-quality trimmed reads were generated from 349 million raw reads, and a total of 114,747 unigenes were obtained after de novo assembly. Furthermore, 95,897 (83.57%) unigenes were annotated to at least one database including NR, Swiss-Prot, KEGG, COG, GO, and NT, supporting that the sequences obtained were annotated properly. Differentially expressed gene analysis indicates that drought stress 15 days could be a critical period for M. sinensis response to drought stress. The high-throughput transcriptome sequencing of M. sinensis under drought stress has greatly enriched the current genomic available resources. The comparison of DEGs under different periods of drought stress identified a wealth of candidate genes involved in drought tolerance regulatory networks, which will facilitate further genetic improvement and molecular studies of the M. sinensis.