|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis显示文摘Current research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis;however,the mechanisms by which this occurs remain poorly understood.Our previous study demonstrated that elevation of microRNA-24(miR-24)in a diabetic setting caused beta cell dysfunction and replicative deficiency.In this study,we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum(ER)stress conditions.We found that miR-24 overabundance protected beta cells from thapsigargin-induced apoptosis at the cost of accelerating the impairment of glucosestimulated insulin secretion(GSIS)and enhancing the presence of dedifferentiation markers.Ingenuity?Pathway Analysis(IPA)revealed that elevation of miR-24 had an inhibitory effect on XBP1 and ATF4,which are downstream effectors of two key branches of ER stress,by inhibiting its direct target,Irela.Notably,elevated miR-24 initiated another pathway that targeted Mafa and decreased GSIS function in surviving beta cells,thus guiding their dedifferentiation under ER stress conditions.Our results demonstrated that the elevated miR-24,to the utmost extent,preserves beta cell mass by inhibiting apoptosis and inducing dedifFerentiation.This study not only provides a novel mechanism by which miR-24 dominates beta cell turnover under persistent metabolic stress but also offers a therapeutic consideration for treating diabetes by inducing dedifferentiated beta cells to re-differentiation. | Yunxia Zhu Yi Sun Yuncai Zhou Yan Zhang Tao Zhang Yating Li Weiyan You Xiaoai Chang Li Yuan Xiao Han | 2019 | Journal of Molecular Cell Biology2019，11，9： | 9 |
| 2 | Haemophilus parasuis infection activates the NF-κB pathway in PK-15 cells through IκB degradation显示文摘 | Yushan Chen Hui Jin Ping Chen Zili Li Xianrong Meng Mei Liu Shaowen Li Deshi Shi Yuncai Xiao Xiliang Wang Zutao Zhou Dingren Bi Rui Zhou | 2012 | Veterinary Microbiology (-)2012，，1： | 1 |
| 3 | Generation and evaluation of sub- 15 fs laser pulses显示文摘 | Zhu Changjun Wang Yuncai Zhou Jianying | 2005 | Chinese Physics2005，17，1： | 1 |
| 4 | HTPdb and HTPtools:Exploiting maize haplotypetag polymorphisms for germplasm resource analyses and genomics-informed breeding显示文摘Along with rapid advances in high-throughput-sequencing technology,the development and application of molecular markers has been critical for the progress that has been made in crop breeding and genetic research.Desirable molecular markers should be able to rapidly genotype tens of thousands of breeding accessions with tens to hundreds of markers.In this study,we developed a multiplex molecular marker,the haplotype-tag polymorphism(HTP),that integrates Maize6H-60K array data from 3,587 maize inbred lines with 6,375 blocks from the recombination block map.After applying strict filtering criteria,we obtained 6,163 highly polymorphic HTPs,which were evenly distributed in the genome.Furthermore,we developed a genome-wide HTP analysis toolkit,HTPtools,which we used to establish an HTP database(HTPdb)covering the whole genomes of 3,587 maize inbred lines commonly used in breeding.A total of 172,921 non-redundant HTP allelic variations were obtained.Three major HTPtools modules combine seven algorithms(e.g.,chain Bayes probability and the heterotic-pattern prediction algorithm)and a new plotting engine named“BCplot”that enables rapid visualization of the background information of multiple backcross groups.HTPtools was designed for big-data analyses such as complex pedigree reconstruction and maize heterotic-pattern prediction.The HTP-based analytical strategy and the toolkit developed in this study are applicable for high-throughput genotyping and for genetic mapping,germplasm resource analyses,and genomics-informed breeding in maize. | Yikun Zhao Hongli Tian Chunhui Li Hongmei Yi Yunlong Zhang Xiaohui Li Han Zhao Yongxue Huo Rui Wang Dingming Kang Yuncai Lu Zhihao Liu Ziyue Liang Liwen Xu Yang Yang Ling Zhou Tianyu Wang Jiuran Zhao Fengge Wang | 2022 | Plant Communications2022，3，4： | 0 |
| 5 | Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation显示文摘During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet(HFD) and streptozotocin(STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of isletβ cells. Cre-LoxP systems were used to generate islet cell type-specific(α, β, or δ) green fluorescent protein(GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing(scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youthand adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these “α or δ” cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis. | Qi Fu Yu Qian Hemin Jiang Yunqiang He Hao Dai Yang Chen Zhiqing Xia Yucheng Liang Yuncai Zhou Rui Gao Shuai Zheng Hui Lv Min Sun Kuanfeng Xu Tao Yang | 2024 | Science China(Life Sciences)2024，67，3： | 0 |
| 6 | BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes显示文摘Brain-specific serine/threonine-protein kinase 2(BRSK2)plays critical roles in insulin secretion andβ-cell biology.However,whether BRSK2 is associated with human type 2 diabetes mellitus(T2DM)has not been determined.Here,we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population.BRSK2 protein levels are significantly elevated inβcells from T2DM patients and high-fat diet(HFD)-fed mice due to enhanced protein stability.Mice with inducibleβ-cell-specific Brsk2 knockout(βKO)exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions.Moreover,βKO mice are protected from HFD-induced hyperinsulinemia,obesity,insulin resistance,and glucose intolerance.Conversely,gain-of-function BRSK2 in matureβcells reversibly triggers hyperglycemia due toβ-cell hypersecretion-coupled insulin resistance.Mechanistically,BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner.The enhanced basal insulin secretion drives insulin resistance andβ-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 inβcells.These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay betweenβcells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions. | Rufeng Xu Kaiyuan Wang Zhengjian Yao Yan Zhang Li Jin Jing Pang Yuncai Zhou Kai Wang Dechen Liu Yaqin Zhang Peng Sun Fuqiang Wang Xiaoai Chang Tengli Liu Shusen Wang Yalin Zhang Shuyong Lin Cheng Hu Yunxia Zhu Xiao Han | 2023 | Journal of Molecular Cell Biology2023，15，5： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员