bioRxiv - Genetics最新文献

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A causative SNP in the promoter of myogenin is essential for myogenic differentiation 肌原蛋白启动子中的一个致病性 SNP 对肌原分化至关重要
bioRxiv - Genetics Pub Date : 2024-08-03 DOI: 10.1101/2024.08.01.606143
Zhuhu Lin, Xiaoyu Wang, Ziyun Liang, Rong Xu, Meilin Chen, Xian Tong, Chenggan Li, Yanyun Xiong, Renqiang Yuan, Yaosheng Chen, Xiaohong Liu, Yunxiang Zhao, Delin Mo
{"title":"A causative SNP in the promoter of myogenin is essential for myogenic differentiation","authors":"Zhuhu Lin, Xiaoyu Wang, Ziyun Liang, Rong Xu, Meilin Chen, Xian Tong, Chenggan Li, Yanyun Xiong, Renqiang Yuan, Yaosheng Chen, Xiaohong Liu, Yunxiang Zhao, Delin Mo","doi":"10.1101/2024.08.01.606143","DOIUrl":"https://doi.org/10.1101/2024.08.01.606143","url":null,"abstract":"Single nucleotide polymorphisms (SNPs) widely existing in different breeds genome represent population-specific. Under the influence of long-term evolution and artificial selection, there are a large number of SNPs between western lean-type pig breeds and Chinese indigenous pig breeds, but until now, little is known about their roles in inter-breed differences. Our study revealed SNP rs3471653254 C>T generated from the two types of pigs mentioned above, located in the promoter shared by MyoG and Myoparr, played an important role in the differentiation of myoblast by influencing the enrichment of HOXA5 to regulate the transcription of MyoG and Myoparr. Meanwhile, Myoparr could be used as the sponge of mir-30b-3p which repressed myogenic differentiation and muscle regeneration through targeting MyoD. Our results indicated that SNP rs3471653254 C>T is essential for myogenic differentiation and regeneration and could be used as an ideal site for increasing lean meat production in pigs.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of vectors for gene expression in Pseudovibrio bacteria and their application in Aplysina marine sponge studies 评估伪弧菌基因表达载体及其在 Aplysina 海洋海绵研究中的应用
bioRxiv - Genetics Pub Date : 2024-08-02 DOI: 10.1101/2024.08.01.606211
Yitao Dai, Lucia Pita, Alessandra S Eustaquio
{"title":"Evaluation of vectors for gene expression in Pseudovibrio bacteria and their application in Aplysina marine sponge studies","authors":"Yitao Dai, Lucia Pita, Alessandra S Eustaquio","doi":"10.1101/2024.08.01.606211","DOIUrl":"https://doi.org/10.1101/2024.08.01.606211","url":null,"abstract":"The filter feeding capacity of marine sponges contributes to biogeochemical cycling and they are also involved in habitat formation, properties that are critical to marine ecology. Sponge-associated microbes are crucial to the functional roles provided by sponges. α-Proteobacteria belonging to the <em>Pseudovibrio</em> genus have been isolated from many different marine sponge genera and have been proposed to contribute to sponge health. We recently reported specialized metabolites we named pseudovibriamides from <em>Pseudovibrio brasiliensis</em> Ab134. The pseudovibriamide encoding <em>ppp</em> gene cluster is found in two thirds of <em>Pseudovibrio</em> genomes. Pseudovibriamides coordinate motility and biofilm formation, behaviors that are known to be important for host colonization. Although reverse genetics methods to delete genes via homologous recombination have been established, no self-replicative vectors have been reported for <em>Pseudovibrio</em>. We show that plasmid vectors containing three different broad-host-range replicons, RSF1010, RK2, and pBBR1, can be used in <em>P. brasiliensi</em>s for fluorescent protein expression and consequent labeling. We then applied GFP and mCherry expressing strains to answer the question of whether pseudovibriamides affect the uptake of <em>P. brasiliensis</em> by <em>Aplysina aerophoba</em> sponges. <em>P. brasiliensis</em> cell counts decreased in the sponge aquaria at an equivalent rate for wild-type and pseudovibriamide-defective Δ<em>pppA</em> mutant strains, indicating that the sponge filters each strain indiscriminately under the conditions tested. Yet, the filtering capacity varied for each sponge individual tested, stressing the importance of performing experiments with wild-type and mutant bacterial strains in the same aquarium to allow for rigorous conclusions, which is now enabled with the methods established here.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of assortative mating and sexual selection on polygenic barriers to gene flow 同配和性选择对基因流动的多基因障碍的影响
bioRxiv - Genetics Pub Date : 2024-07-31 DOI: 10.1101/2024.07.30.605898
Parvathy Surendranadh, Himani Sachdeva
{"title":"Effect of assortative mating and sexual selection on polygenic barriers to gene flow","authors":"Parvathy Surendranadh, Himani Sachdeva","doi":"10.1101/2024.07.30.605898","DOIUrl":"https://doi.org/10.1101/2024.07.30.605898","url":null,"abstract":"Assortative mating and sexual selection are widespread in nature and can play an important role in speciation, through the buildup and maintenance of reproductive isolation (RI). However, their contribution to genome-wide suppression of gene flow during RI is rarely quantified. Here, we consider a polygenic `magic' trait that is divergently selected across two populations connected by migration, while also serving as the basis of assortative mating, thus generating sexual selection on one or both sexes. We obtain theoretical predictions for divergence at individual trait loci by assuming that the effect of all other loci on any locus can be encapsulated via an effective migration rate, which bears a simple relationship to measurable fitness components of migrants and various early generation hybrids. Our analysis clarifies how `tipping points' (characterised by an abrupt collapse of adaptive divergence) arise, and when assortative mating can shift the critical level of migration beyond which divergence collapses. We quantify the relative contributions of viability and sexual selection to genome-wide barriers to gene flow and discuss how these depend on existing divergence levels. Our results suggest that effective migration rates provide a useful way of understanding genomic divergence, even in scenarios involving multiple, interacting mechanisms of RI.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanistic origin and preimplantation development of uniparental and polyploid blastomeres 单亲和多倍体胚泡的机制起源和植入前发育
bioRxiv - Genetics Pub Date : 2024-07-31 DOI: 10.1101/2024.07.30.605883
Yan Zhao, Andrea Fernández-Montoro, Greet Peeters, Tatjana Jatsenko, Tine De Coster, Daniel Angel-Velez, Thomas Lefevre, Thierry Voet, Olga Tšuiko, Ants Kurg, Katrien Smits, Ann Van Soom, Joris Robert Vermeesch
{"title":"Mechanistic origin and preimplantation development of uniparental and polyploid blastomeres","authors":"Yan Zhao, Andrea Fernández-Montoro, Greet Peeters, Tatjana Jatsenko, Tine De Coster, Daniel Angel-Velez, Thomas Lefevre, Thierry Voet, Olga Tšuiko, Ants Kurg, Katrien Smits, Ann Van Soom, Joris Robert Vermeesch","doi":"10.1101/2024.07.30.605883","DOIUrl":"https://doi.org/10.1101/2024.07.30.605883","url":null,"abstract":"Whole-genome (WG) abnormalities, such as uniparental diploidy and triploidy, cause fetal death. Occasionally, they coexist with biparental diploid cells in live births. Understanding the origin and early development of WG abnormal blastomeres is crucial for explaining the formation of androgenotes, gynogenotes, triploidy, chimerism, and mixoploidy. By haplotyping 118 blastomeres from first cleavages, we identified various mechanisms of heterogoneic divisions that lead to WG abnormal blastomeres or their coexistence with normal blastomeres in both multipolar and bipolar cleaving zygotes. After culturing the totipotent blastomeres to three preimplantation stages and performing transcriptome profiling on over 600 cells, we discovered that stress responses contribute to developmental impairment in WG abnormal cells, resulting in either cell arrest or blastocyst formation. However, first-cleavage-derived WG abnormal blastomeres can survive early development and progress to blastocysts. Their potential dominance in preimplantation embryos represents an overlooked cause of abnormal development. Haplotype based screening could further increase pregnancy rates.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic diversity analysis of main agronomic traits and ISSR markers in 35 ornamental rape germplasm resources 35 份观赏油菜种质资源中主要农艺性状和 ISSR 标记的遗传多样性分析
bioRxiv - Genetics Pub Date : 2024-07-30 DOI: 10.1101/2024.07.29.605676
Mang Xia, Meizhu Chen, Xiaoxiao Dong, Miao Chen, Jingdong Chen, Heping Wang, Yuanhuo Dong, Changli Zeng, Xigang Dai, Meizhu Chen,Xiaoxiao Dong, Jingdong Chen, Miao Cheng, Heping Wan, Yuanhuo Dong, Changli Zeng and Xig
{"title":"Genetic diversity analysis of main agronomic traits and ISSR markers in 35 ornamental rape germplasm resources","authors":"Mang Xia, Meizhu Chen, Xiaoxiao Dong, Miao Chen, Jingdong Chen, Heping Wang, Yuanhuo Dong, Changli Zeng, Xigang Dai, Meizhu Chen,Xiaoxiao Dong, Jingdong Chen, Miao Cheng, Heping Wan, Yuanhuo Dong, Changli Zeng and Xig","doi":"10.1101/2024.07.29.605676","DOIUrl":"https://doi.org/10.1101/2024.07.29.605676","url":null,"abstract":"Rape (Brassica napus L.) is a major oil crop in our country, valued for its oil and ornamental uses. This study analyzed 35 ornamental rape germplasm resources from different origins to examine differences in agronomic traits and molecular markers. Nine agronomic traits were assessed in the field for variability, correlation, principal component analysis, and cluster analysis. Genetic diversity was analyzed using microsatellite (ISSR) markers and the unweighted pair group method with arithmetic mean (UPGMA). Our findings revealed a notable average coefficient of variation of 22.59% across the nine agronomic traits, with flower color exhibiting the highest variability and corolla width the least. The observed range of variation spanned from 9.24% to 83.38%, the correlation among these traits was generally low, with a mere 13.9% demonstrating significant correlations. The four principal components accounted for an impressive 84.62% of the cumulative contribution rate, while the genetic similarity, as gauged by eight ISSR primers, varied from 0.675 to 0.980. Most strikingly, we observed that plants from the same geographical region displayed molecular-level differences, underscoring the rich genetic diversity inherent in the 35 ornamental rape resources under study. Employing UPGMA cluster analysis on the primary agronomic traits and ISSR molecular markers, the 35 ornamental rape resources were categorized into seven and four distinct groups, respectively. Although the clustering outcomes from these two methodologies did not align perfectly, they served to complement each other. Collectively, these insights offer a theoretical framework for the innovation of ornamental rape germplasm resources and the cultivation of novel varieties.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR-mediated chromosome deletion facilitates genetic mapping of Vip3Aa resistance gene within complex genomic region in an invasive global pest CRISPR-mediated chromosome deletion facilitates genetic mapping of Vip3Aa resistance gene within complex genomic region in an invasive global pest
bioRxiv - Genetics Pub Date : 2024-07-30 DOI: 10.1101/2024.07.30.605831
Minghui Jin, Yinxue Shan, Yan Peng, Shenlin Chen, Xuanhe Zhou, Kaiyu Liu, Yutao Xiao
{"title":"CRISPR-mediated chromosome deletion facilitates genetic mapping of Vip3Aa resistance gene within complex genomic region in an invasive global pest","authors":"Minghui Jin, Yinxue Shan, Yan Peng, Shenlin Chen, Xuanhe Zhou, Kaiyu Liu, Yutao Xiao","doi":"10.1101/2024.07.30.605831","DOIUrl":"https://doi.org/10.1101/2024.07.30.605831","url":null,"abstract":"Connecting genetic variation to phenotypes and understanding the underlying biological mechanisms has been a fundamental goal of biological genetics. Here, we used the association analysis to identify a Vip3Aa resistance-associated genomic region in a strain of fall armyworm, JC-R, which exhibits &gt;5000-fold resistance to the Bt toxin Vip3Aa. However, through various analytical approaches and fine-scale mapping across different populations, we demonstrated that this genomic region exhibits strong genetic linkage. The chromosome-level genome of JC-R and its parent strain JC-S were assembled, and extensive structural variations in the linkage regions were identified, which could be responsible for maintaining the linkage. To identify the causal variation within this linked region, a chromosome fragment stepwise knockout strategy based on CRISPR/Cas9 was developed. By crossing with the resistant strain and phenotyping segregating offspring on Vip3Aa-containing diet, we identified a chromosomal segment, KO8, containing the resistant gene. Subsequently, we conducted a comprehensive analysis of the variations in the KO8 region using multi-omics approaches, including genomic data, RNA-seq, proteomic, PacBio long read Iso-seq, and phosphoproteomic data. This analysis identified multiple variations in the chitin synthase gene CHS2, including amino acid substitution, alternative splicing, and changes in phosphorylation sites. After knocking out the CHS2, larvae exhibited over 6777-fold resistance to Vip3Aa. These results demonstrate that the chromosome fragment stepwise knockout strategy is a viable approach for studying complex genomic regions, and highlight the value of comprehensive analysis of genetic variations using multi-omics data. The identified candidate gene could potentially advance monitoring and management of pest resistance to Vip3Aa.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic diversity and evolution of rice centromeres 水稻中心粒的遗传多样性和进化
bioRxiv - Genetics Pub Date : 2024-07-29 DOI: 10.1101/2024.07.28.605524
Lingjuan Xie, Yujie Huang, Wei Huang, lianguang Shang, Yanqing Sun, Quanyu Chen, Shuangtian Bi, Mingyu Suo, Shiyu Zhang, Chentao Yang, Xiaoming Zheng, Weiwei Jin, Qian Qian, Longjiang Fan, Wu Dongya
{"title":"Genetic diversity and evolution of rice centromeres","authors":"Lingjuan Xie, Yujie Huang, Wei Huang, lianguang Shang, Yanqing Sun, Quanyu Chen, Shuangtian Bi, Mingyu Suo, Shiyu Zhang, Chentao Yang, Xiaoming Zheng, Weiwei Jin, Qian Qian, Longjiang Fan, Wu Dongya","doi":"10.1101/2024.07.28.605524","DOIUrl":"https://doi.org/10.1101/2024.07.28.605524","url":null,"abstract":"Understanding the mechanisms driving centromere evolution is crucial for deciphering eukaryotic evolution and speciation processes. Despite their widely recognized characteristics of conserved function in cell division, the centromeres have showed high diversity in composition and structure between species. The mechanism underlying this paradox remain poorly understood. Here, we assembled 67 high-quality rice genomes from Oryza AA group, encompassing both Asian and African rice species, and conducted an extensive analysis of over 800 nearly complete centromeres. Through de novo annotation of satellite sequences and employing a progressive compression strategy, we quantified the local homogenization and multi-layer nested structures of rice centromeres and found that genetic innovations in rice centromeres primarily arise from internal structural variations and retrotransposon insertions, along with a certain number of non-canonical satellite repeats (sati). Despite these rapid structural alterations, the single-base substitution rate in rice centromeres appears relatively lower compared to the chromosome arms. Contrary to the KARMA model for Arabidopsis centromere evolution, our model (RICE) suggests that centrophilic LTRs contribute to the decline of progenitor centromeres composed of satellite repeats, and facilitate the formation of evolutionary neo-centromeres, which are enriched with extended CENH3 binding regions beyond the native satellite arrays in plant genomes. In summary, this study provides novel insights into genomic divergence and reproductive barriers among rice species and subspecies, and advances our understanding of plant centromere evolution.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The genetic architecture of resistance to flubendiamide insecticides in Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) Helicoverpa armigera (Hübner)(鳞翅目:夜蛾科)对氟苯地胺杀虫剂抗性的遗传结构
bioRxiv - Genetics Pub Date : 2024-07-28 DOI: 10.1101/2024.07.28.605483
Douglas Amado, Eva L. Koch, Erick M. G. Cordeiro, Wellingson A. Araújo, Antonio Augusto F Garcia, David G. Heckel, Gabriela Montejo-Kovacevich, Henry L. North, Alberto S. Corrêa, Chris D. Jiggins, Celso Omoto
{"title":"The genetic architecture of resistance to flubendiamide insecticides in Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae)","authors":"Douglas Amado, Eva L. Koch, Erick M. G. Cordeiro, Wellingson A. Araújo, Antonio Augusto F Garcia, David G. Heckel, Gabriela Montejo-Kovacevich, Henry L. North, Alberto S. Corrêa, Chris D. Jiggins, Celso Omoto","doi":"10.1101/2024.07.28.605483","DOIUrl":"https://doi.org/10.1101/2024.07.28.605483","url":null,"abstract":"Insecticide resistance is a major problem in food production, environmental sustainability, and human health. The cotton bollworm <em>Helicoverpa armigera</em> is a globally distributed crop pest affecting over 300 crop species. <em>H. armigera</em> has rapidly evolved insecticide resistance, making it one of the most damaging pests worldwide. Understanding the genetic basis of insecticide resistance provides insights to develop tools, such as molecular markers, that can be used to slow or prevent the evolution of resistance. We explore the genetic architecture of <em>H. armigera</em> resistance to a widely used insecticide, flubendiamide, using two complementary approaches: genome-wide association studies (GWAS) in wild-caught samples and quantitative trait locus (QTL) mapping in a controlled cross of susceptible and resistant laboratory strains. Both approaches identified one locus on chromosome 2, revealing two SNPs within 976 bp that can be used to monitor field resistance to flubendiamide. This was the only region identified using linkage mapping, though GWAS revealed additional sites associated with resistance. Other loci identified by GWAS in field populations contained known insecticide detoxification genes from the <em>ATP-binding cassette</em> family, ABCA1, ABCA3, ABCF2 and MDR1. Our findings revealed an oligogenic genetic architecture, in contrast to previous reports of monogenic resistance associated with the <em>ryanodine receptor</em>. This work elucidates the genetic basis of rapidly evolving insecticide resistance and will contribute to the development of effective insecticide resistance management strategies.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping the peripheral immune landscape of Parkinson's disease patients with single-cell sequencing 利用单细胞测序绘制帕金森病患者的外周免疫图谱
bioRxiv - Genetics Pub Date : 2024-07-28 DOI: 10.1101/2024.07.26.605020
Gael Moquin-Beaudry, Lovatiana Andriamboavonjy, Sebastien Audet, Laura Hamilton, Antoine Duquette, Sylvain Chouinard, Michel Panisset, Martine Tetreault
{"title":"Mapping the peripheral immune landscape of Parkinson's disease patients with single-cell sequencing","authors":"Gael Moquin-Beaudry, Lovatiana Andriamboavonjy, Sebastien Audet, Laura Hamilton, Antoine Duquette, Sylvain Chouinard, Michel Panisset, Martine Tetreault","doi":"10.1101/2024.07.26.605020","DOIUrl":"https://doi.org/10.1101/2024.07.26.605020","url":null,"abstract":"Parkinson's Disease (PD) is widely recognized for its impact on the central nervous system. Recent breakthroughs underscore the crucial role of interactions between central and peripheral systems in PD's pathogenesis, highlighting the need for a paradigm shift in PD research. The spotlight is now shifting as we explore beyond the central nervous system, discovering that peripheral changes such as inflammatory dysfunctions may predict the rate of disease progression and severity. However, the cellular mechanisms driving these immunity changes remain largely unknown. Despite over 200 years of research on PD, robust diagnostic or progression biomarkers and disease altering therapeutics are still lacking. Thus, understanding peripheral immune signatures could lead to earlier diagnosis and more effective treatments for PD. Here, we sought to define the transcriptomic alterations of the complete peripheral immune cell compartment by single-cell RNA- and T-cell receptor-sequencing with hopes of uncovering PD signatures and potential peripheral blood biomarkers. Following transcriptional profiling of 78 876 cells from 10 healthy controls and 14 PD donors, we observed five major classes of immune cell types; myeloid (monocytes, dendritic cells) and lymphoid (T, B, natural killer) cells from which we identified 38 cellular subtypes following bioinformatic re-clustering. Comparing immune cell subtypes and phenotypes between PD patients and healthy controls revealed notable features of PD: 1) a significant shift of classical CD14+ monocytes towards an activated CD14+/CD83+ state, 2) changes in lymphocyte subtypes abundance, including a significant decrease in CD4+ naive and mucosal-associated invariant T-cells subtypes, along with an increase in CD56+ natural killer cells, 3) the identification by T-cell receptor sequencing of several PD specific T-cell clones shared between multiple patients, suggesting the implication of common epitopes in PD pathogenesis, 4) a notable increase in the expression of activation signature genes, including the AP-1 stress-response transcription factor complex, across all PD cell types. This signal was not present in atypical Parkinsonism patients with multiple systems atrophy or progressive supranuclear palsy. Overall, we present a comprehensive atlas of peripheral blood mononuclear cells from control and PD patients which should serve as a tool to improve our understanding of the role the immune cell landscape plays in PD pathogenesis.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex Dimorphism in Expression of Immune Response Genes in Drosophila 果蝇免疫反应基因表达的性别二态性
bioRxiv - Genetics Pub Date : 2024-07-27 DOI: 10.1101/2024.07.27.605461
MD Mursalin Khan, Rita M. Graze
{"title":"Sex Dimorphism in Expression of Immune Response Genes in Drosophila","authors":"MD Mursalin Khan, Rita M. Graze","doi":"10.1101/2024.07.27.605461","DOIUrl":"https://doi.org/10.1101/2024.07.27.605461","url":null,"abstract":"Sex dimorphism in immunity is commonly observed in a wide variety of taxa and is thought to arise from fundamental life history differences between females and males. In Drosophila melanogaster, infection with different pathogens typically results in different modes of immune sex dimorphism, with male- or female-bias, likely due to specific disease-causing mechanisms of pathogens and host-pathogen interactions. Studies showed that some pathways, such as IMD and Toll, can explain these sex-dimorphic immune responses in Drosophila. However, it is unclear if sex differences in the immune response observed in D. melanogaster are conserved, even in closely related species. One window into identifying conserved and evolving sex differences in the immune response is to examine the sex-differential expression of immunity-related genes. Here, we aim to understand whether two closely related species, D. melanogaster and D. simulans, show conserved sex dimorphism in innate immunity, focusing on associated changes in gene expression in response to infection with a gram-negative bacterium, Providencia rettgeri. Survival, bacterial load, and bacterial load upon death (BLUD) were investigated to assess overall sex differences. D. melanogaster females and males differed significantly in survival, whereas D. simulans did not. Enrichment analyses revealed that both sexes and species upregulate genes involved in similar immune-related biological processes, but downregulated groups differed. We identified conserved sex differential gene expression of genes in the bacterial infection response pathways IMD, Toll, Jak/STAT, their regulators, and other immune-related gene classes (e.g., BOMs), as well as sex and species differences. In D. melanogaster, the effector antimicrobial peptides (AMPs) regulated by IMD were more highly upregulated relative to D. simulans in both sexes. Moreover, D. melanogaster females uniquely initiated high levels of gene expression that were involved in negative feedback mechanisms that controlled the overstimulation of IMD. Genes in the Toll pathway were also sex-differentially expressed with a higher level of upregulation in D. melanogaster. Remarkably, comparing expression across species, we find that D. simulans likely employs both the conventional peptidoglycan recognition-driven PRR-SPE-Spz pathway and the microbial protease recognition-based Psh-dependent activation of Toll; in contrast, D. melanogaster appears to solely rely on the PRR-SPE-Spz pathway in this context. In summary, our findings indicate that sex differences are conserved in both species for the majority of upregulated genes, while downregulation patterns and specific gene subsets show notable differences between sexes or species.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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