Biology subjects

Ni, C.

Publications and source records attributed to Ni, C..

21 records · Page 2Linked to original sources

bioRxiv2020

Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Organoids

The newly emerged pandemic coronavirus, SARS-CoV-2, has posed a significant public health threat worldwide. However, the mode of virus transmission and tissue tropism is not well established yet. Recent findings of substantial liver damage in patients and ACE2+ cholangiocytes in healthy liver tissues prompted us to hypothesize that human liver ductal organoids could serve as a model to determine the susceptibility and mechanisms underlining the liver damage upon SARS-CoV-2 infection. By single-cell RNA sequencing, we found that long-term liver ductal organoid culture preserved the human specific ACE2+ population of cholangiocytes. Moreover, human liver ductal organoids were permissive to SARS-CoV-2 infection and support robust replication. Notably, virus infection impaired the barrier and bile acid transporting functions of cholangiocytes through dysregulation of genes involved in tight junction formation and bile acid transportation, which could explain the bile acid accumulation and consequent liver damage in patients. These results indicate that control of liver damage caused directly by viral infection should be valued in treating COVID-19 patients. Our findings also provide an application of human organoids in investigating the tropism and pathogenesis of SARS-CoV-2, which would facilitate novel drug discovery.

cell biology↗

bioRxiv2019

Efficient and accurate prediction of transmembrane topology from amino acid sequence only

MotivationRapid and accurate identification of transmembrane (TM) topology is well suited for the annotation of the entire membrane proteome. It is the initial step of predicting the structure and function of membrane proteins. However, existing methods that utilize only amino acid sequence information suffer from low prediction accuracy, whereas methods that exploit sequence profile or consensus need too much computational time.\n\nMethodHere we propose a deep learning framework DeepCNF that predicts TM topology from amino acid sequence only. Compared to previous sequence-based approaches that use hidden Markov models or dynamic Bayesian networks, DeepCNF is able to incorporate much more contextual information by a hierarchical deep neural network, while simultaneously modeling the interdependency between adjacent topology labels.\n\nResultExperimental results show that PureseqTM not only outperforms existing sequence-based methods, but also reaches or even surpasses the profile/consensus methods. On the 39 newly released membrane proteins, our approach successfully identifies the correct TM segments and boundaries for at least 3 cases while all existing methods fail to do so. When applied to the entire human proteome, our method can identify the incorrect annotations of TM regions by UniProt and discover the membrane-related proteins that are not manually curated as membrane proteins.\n\nAvailabilityhttp://pureseqtm.predmp.com/

bioinformatics↗

bioRxiv2017

A Rice Dual-localized Pentatricopeptide Repeat Protein is involved in Organellar RNA Editing with MORFs

Flowering plants engage in diverse RNA editing events in mitochondrion and chloroplast on post-transcriptional process. Although several PPRs and MORFs were identified as RNA editing factors, the underlying mechanism of PPRs and the cooperation among them are still obscure. Here, we identified a rice dual-localized PPR mutant Ospgl1. Loss-of-function of OsPGLl resulted in defect of chloroplast RNA editing at ndhD-878 and mitochondrial RNA editing at ccmFc-543, which can be restored via complementary validation. Despite the synonymous editing on ccmFc-543, loss of editing at ndhD-878 caused failure of conversion from serine to leucine, leading to the dysfunction of chloroplast and defective in photosynthetic complex, further studies demonstrated OsPGL1 directly bound to both two transcripts. The interaction between three MORFs (MORF2/8/9) and OsPGL1 were confirmed in vitro and in vivo, implied OsPGL1 functioned on RNA editing via an editosome. It also suggested MORFs assisted and contributed to the flexible PPR-RNA recognition model during RNA editing through the cooperation with PPRs. These results provide new insight into the relationship between RNA editing and plant development on chloroplast.\n\nHighlightWe firstly characterized a dual-localized PPR protein which is required for RNA editing in mitochondrion and chloroplast simultaneously. OsPGL1 binds to two distinguish target transcripts directly and cooperated with MORFs.

molecular biology↗