Biology subjects

Li, Y.-X.

Publications and source records attributed to Li, Y.-X..

4 recordsLinked to original sources

bioRxiv2021

A dual reporter system identifies an intermediate state and sequential regulators of 2-cell-like-to-pluripotent state transition

Mouse embryonic stem cells (ESCs) cycle in and out of 2-cell-like (2C-like) state in culture. The molecular mechanism governing the exit of 2C-like state remains obscure, partly due to the lack of a reporter system that can genetically mark intermediate states during exiting process. Here, we identify an intermediate state that is marked by the co-expression of MERVL::tdTomato and OCT4-GFP (MERLOT) during 2C-like-to-pluripotent state transition (2CLPT). Transcriptome and epigenome analyses demonstrate that MERLOT cells cluster closely with 8-16 cell stage mouse embryos, suggesting that 2CLPT partly mimics early preimplantation development. Through a CRISPRa screen, we identify an ARRDC3-NEDD4-OCT4 regulatory axis that plays an essential role in controlling 2CLPT. Furthermore, re-evaluating previously reported 2C-like state regulators reveals dual function of Chaf1a in regulating the entry and exit of 2C-like state. Finally, ATAC-Seq footprinting analysis uncovers Klf3 as an essential transcription factor required for efficient 2CLPT. Together, our study identifies a genetically traceable intermediate state during 2CLPT and provides a valuable tool to study molecular mechanisms regulating this process.

cell biology↗

bioRxiv2021

Correlational networking guides the discovery of cryptic proteases for lanthipeptide maturation

Bacterial natural product biosynthetic genes, canonically clustered, have been increasingly found to rely on cryptic enzymes encoded elsewhere in the genome for completion of biosynthesis. The study and application of lanthipeptides are frequently hindered by cryptic proteases required for final maturation. Here, we establish a global correlation network bridging the gap between lanthipeptide precursors and cryptic proteases. Applying our analysis to 161,954 bacterial genomes, we establish 5,209 correlations between precursors and cryptic proteases, with 91 prioritized. We use network predictions and co-expression analysis to reveal a previously missing protease for the maturation of class I lanthipeptide paenilan. We further discover widely distributed bacterial M16B metallopeptidases of previously unclear biological function as a new family of lanthipeptide proteases. We show the involvement of a pair of bifunctional M16B proteases in the production of novel class III lanthipeptides with high substrate specificity. Together, these results demonstrate the strength of our correlational networking approach to the discovery of cryptic lanthipeptide proteases and potentially other missing enzymes for natural products biosynthesis. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biochemistry↗

bioRxiv2020

Virulence evolution of multiple infections with vertically and horizontally transmitted fungal species in a natural plant system

The virulence evolution of multiple infections of parasites from the same species has been modelled widely in evolution theory, and the trajectories of evolution are relevant to parasite transmission mode, as well as to parasite and host population dynamics. However, experimental studies on this topic remain scarce, particularly regarding multiple infections by different parasite species. In this study, we employed the invasive plant Ageratina adenophora to verify the predictions made by the model. We observed that A. adenophora was a highly susceptible host to phylogenetically diverse foliar pathogens with mixed vertical and horizontal transmission within leaf spots. The pathogen community structure at the leaf spot level was determined by transmission mode. Over time, the pathogen community decreased in diversity; meanwhile, the vertically transmitted pathogens exhibited decreased virulence to the host A. adenophora, but the horizontally transmitted pathogens exhibited increased virulence to the host. Our results demonstrate that the predictions of classical models are still valid in a complex environment. Moreover, we propose that it is very important to determine whether the primary foliar pathogen of a given plant host is relevant to seedborne fungi, as this characteristic is an important factor in understanding pathogen-host interactions.

ecology↗

bioRxiv2020

The diagnostic value of RASSF1A promoter methylation in prostate cancer: A systematic review and meta-analysis

BackgroundRASSF1A promoter methylation is consistent with clinicopathological data and has good accuracy in distinguishing tumors. However, the diagnostic parameters vary among previous studies. A systematic review was conducted to explore the diagnostic value of RASSF1A promoter methylation in prostate cancer. MethodsA comprehensive search of the literature in the PubMed, Medline, Cochrane Library, Embase and ISI Web of Science databases up to May 21, 2020 was performed. STATA software version 12.0 and Meta-disc version 1.4 were used to analyze the data. ResultsThe pooled sensitivity was 0.64 (95% CI 0.61-0.66), the pooled specificity was 0.80 (95% CI 0.77-0.83), the PLR was 3.82 (95% CI 1.96-7.44), and the NLR was 0.29 (95% CI 0.16-0.52). Furthermore, the pooled DOR of RASSF1A promoter methylation for prostate cancer was 13.08 (95% CI: 6.56-26.08). The area under the summary ROC curve was 0.87 (95% CI: 0.84-0.90). The results of the meta-regression suggested that heterogeneity was mainly derived from publication year. Fagans nomogram showed that the predictive accuracy was increased significantly by detecting RASSF1A promoter methylation for diagnosing prostate cancer. ConclusionThis meta-analysis suggests that detection of the RASSF1A promoter methylation status can be used for the diagnosis of PCa. In the future, further analyses and studies of larger sample sizes in large centers are needed to confirm our conclusion.

cancer biology↗