Biology subjects

Jiao, B.

Publications and source records attributed to Jiao, B..

6 recordsLinked to original sources

bioRxiv2023

Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin-antidote gene drive that impairs pollen germination

Synthetic gene drives, inspired by natural selfish genetic elements, present transformative potential for disseminating traits that benefit humans throughout wild populations, irrespective of potential fitness costs. Here, we constructed a gene drive system called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which employs a toxin-antidote mechanism in the male germline to override Mendelian inheritance in plants. Specifically, a gRNA-Cas9 cassette targets the essential No Pollen Germination 1 (NPG1) gene, serving as the toxin to block pollen germination. A recoded, CRISPR-resistant copy of NPG1 serves as the antidote, providing rescue only in pollen cells that carry the drive. To limit potential consequences of inadvertent release, we used self-pollinating Arabidopsis thaliana as a model. The drive demonstrated a robust 88-99% transmission rate over two successive generations, producing minimal resistance alleles that are unlikely to inhibit drive spread. Our study provides a strong basis for rapid genetic modification or suppression of outcrossing plant populations.

evolutionary biology↗

bioRxiv2023

Histone deacetylase 3 plays a critical role in hypertension-induced kidney inflammation and fibrosis

Objective: Hypertension is a major cause of chronic kidney disease. The molecular mechanisms how hypertension causes kidney disease are not fully understood. In this study, we examined the functional role of histone deacetylase 3 (HDAC3) in the pathogenesis of hypertensive kidney disease. Approach and Results: Myeloid HDAC3 knockout mice were generated by crossing HDAC3f/f mice with LysM-Cre+/- mice. Both LysM-Cre-/-HDAC3f/f (HDAC3CON) mice and LysM-Cre+/+HDAC3f/f (HDAC3MKO) mice were subjected to uninephrectomy and treated with angiotensin II at 1.5 ug/kg/min or vehicle for 28 days. Blood pressure increased comparably in both HDAC3CON and HDAC3MKO mice following angiotensin II treatment. Compared with HDAC3CON mice, HDAC3MKO mice were protected from angiotensin II-induced kidney dysfunction and pathological injury and developed less proteinuria. Myeloid HDAC3 deficiency markedly attenuated the protein levels of fibronectin, collagen I, and ?-SMA in the kidney following angiotensin II treatment. Furthermore, HDAC3MKO mice accumulated significantly fewer myeloid fibroblasts and macrophages in the kidney after angiotensin II treatment. Myeloid HDAC3 deficiency significantly reduced the mRNA expression of proinflammatory molecules in the kidney following angiotensin II treatment. In cultured macrophages, knockdown of HDAC3 with shRNA suppressed proinflammatory molecule expression. Furthermore, knockdown of HDAC3 inhibited NF-kB p65 enrichment to IL-6 promoter. Conclusion: Our study identifies a critical role of myeloid HDAC3 in the regulation of hypertension-induced kidney inflammation and fibrosis. Targeting HDAC3 may represent a novel therapeutic strategy for hypertensive kidney disease.

pathology↗

bioRxiv2021

WGDI: A user-friendly toolkit for evolutionary analyses of whole-genome duplications and ancestral karyotypes

Evidence of whole-genome duplications (WGDs) and subsequent karyotype changes has been detected in most major lineages of life on Earth. To clarify the complex resulting multiple-layered patterns of gene collinearity in genome analyses there is a need for convenient and accurate toolkits. To meet this need, we introduce here WGDI (Whole-Genome Duplication Integrated analysis), a Python-based command-line tool that facilitates comprehensive analysis of recursive polyploidizations and cross-species genome alignments. WGDI supports three main workflows (polyploid inference, hierarchical inference of genomic homology, and ancestral chromosomal karyotyping) that can improve detection of WGD and characterization of related events. It incorporates a more sensitive and accurate collinearity detection algorithm than previous softwares, and can accelerate WGD-related karyotype research. As a freely available toolkit at GitHub (https://github.com/SunPengChuan/wgdi), WGDI outperforms similar tools in terms of efficiency, flexibility and scalability. In an illustrative example of its application, WGDI convincingly clarified karyotype evolution in Aquilegia coerulea and Vitis vinifera following WGDs and rejected the hypothesis that Aquilegia contributed as a parental lineage to the allopolyploid origin of core dicots.

bioinformatics↗

bioRxiv2018

Study of the binding mechanisms between palytoxin and its aptamer by docking and molecular simulation

This paper provides a feasible model for aptamer and its target in molecular structure analysis and interaction mechanism. In this study, modeling and dynamic simulation of ssDNA aptamer (P-18S2) and target (Palytoxin, PTX) were performed separately. Then, the combination mechanism of DNA and PTX were predicted, and docking results showed that PTX can combine steadily in the groove at the top of DNA model trough strong hydrogen-bonds and electrostatic interaction. Therefore, we have further truncated and optimized to P-18S2 by simulating, at the same time, we also confirmed the reliability of simulative results by experimenting. Combining with the experimental and computational results, we provide a more reasonable interpretation for the high affinity and specific binding of P-18S2 and PTX and offer the basis for aptamer development in molecular diagnostics and therapeutic application.\n\nAuthor summaryIn order to further study the complex structure and interaction of P-18S2 and PTX, a series of molecular modeling program were designed, including modeling, traditional dynamics simulation and molecular docking. Modeling results reveal that the structure of P-18S2 is a DNA G-quadruplex. Meanwhile, the 3D structure of PTX with lowest total energy after equilibrium was selected to use for the subsequent simulations. Then, based on the DNA with G-quadruplex structure, the combination model of DNA and PTX were predicted, and docking results showed that PTX can combine steadily in the groove at the top of DNA model trough strong hydrogen-bonds and electrostatic interaction. Futhermore, we compared the affinity of 6 optimized aptamers by computer simulating to primary P-18S2 bind to PTX respectively, the results showed no significant difference. Therefore, we have further truncated and optimized to P-18S2. In addition, this paper further refined research method based on our previous study[17], the instability of the target structure was considered and optimized, and the biological experiments were used to confirm the veracity of the simulative results. Combining with the experimental and computational methods, we obtained a reasonable interpretation for the high affinity and specific binding of P-18S2 and PTX. In summary, we established a feasible model for aptamer and its target in molecular structure analysis and interaction mechanism, and offer the basis for the study of aptamer development in molecular diagnostics and therapeutic application.

molecular biology↗

bioRxiv2017

Systematic Analysis Of RNA-Seq-Based Gene Co-Expression Across Multiple Plants

The complex cellular network was formed by the interacting gene modules. Building the high-quality RNA-seq-based Gene Co-expression Network (GCN) is critical for uncovering these modules and understanding the phenotypes of an organism. Here, we established and analyzed the RNA-seq-based GCNs in two monocot species rice and maize, and two eudicot species Arabidopsis and soybean, and subdivided them into co-expressed modules. Taking rice as an example, we associated these modules with biological functions and agronomic traits by enrichment analysis, and discovered a large number of conditin-specific or tissue-specific modules. In addition, we also explored the regulatory mechanism of the modules by enrichment of the known cis-elements, transcription factors and miRNA targets. Their coherent enrichment with the inferred functions of the modules revealed their synergistic effect on the gene expression regulation. Moreover, the comparative analysis of gene co-expression was performed to identify conserved and species-specific functional modules across 4 plant species. We discovered that the modules shared across 4 plants participate in the basic biological processes, whereas the species-specific modules were involved in the spatiotemporal-specific processes linking the genotypes to phenotypes. Our research provides the massive modules relating to the cellular activities and agronomic traits in several model and crop plant species.

bioinformatics↗

bioRxiv2017

High-Quality Rice RNA-Seq-Based Co-Expression Network For Predicting Gene Function And Regulation

Inferring the genome-scale gene co-expression network is important for understanding genetic architecture underlying the complex and various biological phenotypes. The recent availability of large-scale RNA-seq sequencing-data provides great potential for co-expression network inference. In this study, for the first time, we presented a novel heterogeneous ensemble pipeline integrating three frequently used inference methods, to build a high-quality RNA-seq-based Gene Co-expression Network (GCN) in rice, an important monocot species. The quality of the network obtained by our proposed method was first evaluated and verified with the curated positive and negative gene functional link datasets, which obviously outperformed each single method. Secondly, the powerful capability of this network for associating unknown genes with biological functions and agronomic traits was showed by enrichment analysis and case studies. Particularly, we demonstrated the potential applications of our proposed method to predict the biological roles of long non-coding RNA (lncRNA) and circular RNA (circRNA) genes. Our results provided a valuable data source for selecting candidate genes to further experimental validation during rice genetics research and breeding. To enhance identification of novel genes regulating important biological processes and agronomic traits in rice and other crop species, we released the source code of constructing high-quality RNA-seq-based GCN and rice RNA-seq-based GCN, which can be freely downloaded online at https://github.com/czllab/NetMiner.

bioinformatics↗