Currently, Illumina sequencers are the globally leading sequencing platform in the next-generation sequencing market. Recently, MGI Tech launched a series of new sequencers, including the MGISEQ-2000, which promise to deliver high-quality sequencing data faster and at lower prices than Illumina's sequencers. In this study, we compared the performance of two major sequencers (MGISEQ-2000 and HiSeq 4000) to test whether the MGISEQ-2000 sequencer delivers high-quality sequence data as suggested. We performed RNA sequencing of four human colon cancer samples with the two platforms, and compared the sequencing quality and expression values. The data produced from the MGISEQ-2000 and HiSeq 4000 showed high concordance, with Pearson correlation coefficients ranging from 0.98 to 0.99. Various quality control (QC) analyses showed that the MGISEQ-2000 data fulfilled the required QC measures. Our study suggests that the performance of the MGISEQ-2000 is comparable to that of the HiSeq 4000 and that the MGISEQ-2000 can be a useful platform for sequencing.

Significance: The molecular mechanisms by which gut microbes modulate host longevity remain elusive. Using genome-wide lifespan screens and extensive interspecies genetic analysis, we identified that the gut microbe-derived metabolite methylglyoxal (MG) modulated host longevity. MG is a reactive carbonyl species involved in the formation of advanced glycation end products, which are implicated in various human pathologies. We identified that Escherichia coli producing reduced levels of MG increased the lifespan of Caenorhabditis elegans due to inhibition of TORC2/SGK-1 and activation of DAF-16. These findings challenge the current paradigm that MG is toxic due to the formation of glycation adducts on biomolecules. Instead, our results highlight the importance of gut microbe-derived MG in regulating the host TORC2/SGK-1/DAF-16 signaling pathway in the interspecies context.

Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion-positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance, as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). Although drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. In this study, we used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the naïve cell population by scRNA-seq, and their abundance was increased in the acquired-resistance population. Knockdown of CDA had antiproliferative effects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2′-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Collectively, our data suggest that targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK inhibitor resistance in NSCLC.

Bi-Oh Park, Seong Heon Kim, Jong Hwan Kim, Seon-Young Kim, Byoung Chul Park, Sang-Bae Han, Sung Goo Park, Jeong-Hoon Kim, and Sunhong Kim. Mol. Cells 2021;44:458-67. https://doi.org/10.14348/molcells.2021.0021

Previous studies have reported that vitamin C (VC) promotes neural stem/precursor cell (NSC) differentiation toward dopamine (DA) neurons via DNA hydroxymethylation-induced transcriptional activation of DA neuron-specific genes. To further understand the VC effects on NSC differentiation, we profiled the transcriptome and DNA methylome/hydroxymethylome using high-throughput sequencing. Interestingly, RNA sequencing analyses have shown that, in addition to DA neuronal genes, astrocytic genes Gfap, Slc1a3, and S100a16 were also upregulated in NSC cultures differentiated with VC treatment. Consistently, enhanced GFAP+ astrocytic yields were manifested in the differentiated cultures with VC treatment, collectively indicating that VC promotes astrocytic differentiation. In genome-wide hydroxymethylome analyses, VC treatment induces enrichment of DNA hydroxymethylation (5-hydroxymethyl cytosine; 5hmC) near the consensus binding motifs of nuclear factor I (NFI). Furthermore, we showed that VC significantly enhanced recruitment of NFI and STAT3, key transcription factors for astrogenesis, in the 5hmC-enriched regions of the astrocyte-specific genes. These findings suggest that VC play important roles in astrocytogenesis during brain development. Stem Cells 2018;36:1578–1588

Mijin Park, Byul Moon, Jong-Hwan Kim, Seung-Jin Park, Seon-Kyu Kim, Kihyun Park, Jaehoon Kim, Seon-Young Kim, Jeong-Hoon Kim, and Jung-Ae Kim. Mol. Cells 2022;45:550-63. https://doi.org/10.14348/molcells.2022.0009