Characterizing single cell states of activated and transformed B cells in rhesus macaque models
恒河猴模型中活化和转化 B 细胞的单细胞状态特征
基本信息
- 批准号:10665491
- 负责人:
- 金额:$ 23.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-02 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAddressArchivesAreaB-Cell Acute Lymphoblastic LeukemiaB-Cell DevelopmentB-Cell LymphomasB-LymphocytesB-cell receptor repertoire sequencingBiologicalCRISPR screenCancer BurdenCancerousCell Culture TechniquesCell LineCell surfaceCellsCellular Indexing of Transcriptomes and Epitopes by SequencingDependenceDevelopmentDiagnosticDifferentiation AntigensDimensionsDiseaseEBV-associated diseaseEnvironmentEpstein Barr Nuclear Antigen 3Epstein-Barr Virus InfectionsEpstein-Barr Virus-Related Malignant NeoplasmEpstein-Barr pathogenesisGene ExpressionGenetic TranscriptionGoalsGrowthHeterogeneityHumanHuman Herpesvirus 4IRF4 geneImmuneImmunocompromised HostImmunophenotypingIn VitroIndividualInfectionInfectious AgentIntegration Host FactorsKnowledgeLMP1LinkLongitudinal StudiesLymph Node TissueLymphocryptovirusLymphoid TissueLymphomaLymphoproliferative DisordersMS4A1 geneMacaca mulattaMalignant NeoplasmsMapsMeasuresMediatingMethodsMicroRNAsModelingMolecularMolecular ProfilingNaturePathway interactionsPatientsPre-Clinical ModelPredispositionProcessProliferatingProliferation MarkerPropertyRefractoryResolutionResourcesRestRhesusSamplingSideTechniquesTherapeuticTumor AntigensTumor TissueViralViral CancerViral ProteinsVirusVirus Diseasescell transformationchronic infectionexperimental studygammaherpesvirusgene productgenetic manipulationgenetic signatureimmune checkpointimprovedin vivoinfected B cellinfectious disease modellatent infectionlymphoblastoid cell linemolecular dynamicsmolecular markermultiple omicsmutantpermissivenesspre-clinicalpremalignantprogramssingle-cell RNA sequencingtime usetranscription factortranscriptometranscriptome sequencingtranscriptomicstumortumor heterogeneity
项目摘要
Project Summary
Epstein-Barr virus (EBV) causes significant disease in patients with congenital or acquired immune deficiencies.
Elucidating markers of early cancer and understanding tumor composition are essential in improving diagnostics
and therapies for EBV diseases. In vitro, EBV infection of B cells induces formation of lymphoblastoid cell lines
(LCLs) which mimic properties of lymphoproliferative disease and serve as a model to investigate B cell
transformation processes. Multiple viral gene products dramatically reprogram the B cell environment, and
several host factors critical for maintaining LCL proliferation have been identified; however, host factors leading
to LCL outgrowth as well as the distinct cellular substages required for establishment of persistent infection and
B cell transformation are less understood. Deciphering the molecular mechanisms involved in these processes
is an ongoing challenge due to the refractory nature of primary B cells for genetic manipulation and the observed
heterogeneity in viral and cellular gene expression detected through standard bulk transcriptome analysis. To
address gaps in our current knowledge, we will use multi-omic single-cell approaches to define B cell molecular
signatures and cell markers that delineate early virus-mediated transformation. For these studies, we will
investigate a pre-clinical EBV model, rhesus macaque (RM) cells and tumor tissues infected with rhesus
lymphocryptovirus (rLCV). By simultaneously measuring immunophenotypes and gene expression, we aim to
identify B cell states that successfully navigate infection towards the LCL trajectory. Leveraging these
approaches to further analyze rLCV+ lymphoid tissues, we aim to define biological properties of pre-cancerous
and cancerous states at the single cell level.
项目摘要
EB病毒(EBV)在先天性或获得性免疫缺陷患者中引起重大疾病。
阐明早期癌症的标志物和了解肿瘤的组成对于改善诊断至关重要
和治疗EBV疾病的方法。在体外,EBV感染B细胞诱导淋巴母细胞系的形成
(LCL),其模拟淋巴组织增生性疾病的性质并用作研究B细胞的模型
转化过程。多种病毒基因产物显著地重新编程B细胞环境,
已经确定了几个维持LCL增殖的关键宿主因素;然而,
LCL生长以及建立持续感染所需的不同细胞亚阶段,
对B细胞转化了解较少。破译这些过程中涉及的分子机制
由于原代B细胞对于遗传操作的难治性和观察到的
通过标准批量转录组分析检测病毒和细胞基因表达的异质性。到
为了填补我们现有知识的空白,我们将使用多组学单细胞方法来定义B细胞分子
描述早期病毒介导的转化的特征和细胞标志物。对于这些研究,我们将
研究EB病毒临床前模型、恒河猴(RM)细胞和恒河猴感染肿瘤组织
淋巴隐病毒(rLCV)。通过同时测量免疫表型和基因表达,我们的目标是
识别成功地将感染导向LCL轨迹的B细胞状态。利用这些
为了进一步分析rLCV+淋巴组织,我们的目标是定义癌前病变的生物学特性。
和癌细胞的状态。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rebecca L Skalsky其他文献
Analysis of the miRNA targetome in EBV-infected B cells
- DOI:
10.1186/1750-9378-7-s1-o2 - 发表时间:
2012-04-19 - 期刊:
- 影响因子:2.800
- 作者:
Rebecca L Skalsky;David L Corcoran;Eva Gottwein;Christopher L Frank;Markus Hafner;Jeffrey D Nusbaum;Regina Feederle;Henri-Jacques Delecluse;Micah Luftig;Thomas Tuschl;Uwe Ohler;Bryan R Cullen - 通讯作者:
Bryan R Cullen
Rebecca L Skalsky的其他文献
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{{ truncateString('Rebecca L Skalsky', 18)}}的其他基金
Regulation of host miRNA activity by Epstein-Barr virus BHRF1
Epstein-Barr 病毒 BHRF1 对宿主 miRNA 活性的调节
- 批准号:
10170258 - 财政年份:2020
- 资助金额:
$ 23.62万 - 项目类别:
Regulation of host miRNA activity by Epstein-Barr virus BHRF1
Epstein-Barr 病毒 BHRF1 对宿主 miRNA 活性的调节
- 批准号:
10039435 - 财政年份:2020
- 资助金额:
$ 23.62万 - 项目类别:
microRNA Regulation of Gamma-herpesvirus Latency and Reactivation
microRNA 对 γ-疱疹病毒潜伏期和再激活的调节
- 批准号:
10532215 - 财政年份:2019
- 资助金额:
$ 23.62万 - 项目类别:
microRNA Regulation of Gamma-herpesvirus Latency and Reactivation
microRNA 对 γ-疱疹病毒潜伏期和再激活的调节
- 批准号:
10084264 - 财政年份:2019
- 资助金额:
$ 23.62万 - 项目类别:
microRNA Regulation of Gamma-herpesvirus Latency and Reactivation
microRNA 对 γ-疱疹病毒潜伏期和再激活的调节
- 批准号:
10319587 - 财政年份:2019
- 资助金额:
$ 23.62万 - 项目类别:
The role of viral and cellular miRNAs in B-cell lymphomagenesis
病毒和细胞 miRNA 在 B 细胞淋巴瘤发生中的作用
- 批准号:
8634961 - 财政年份:2014
- 资助金额:
$ 23.62万 - 项目类别:
The Role of Viral and Cellular miRNAs in B-cell Lymphomagenesis
病毒和细胞 miRNA 在 B 细胞淋巴瘤发生中的作用
- 批准号:
9334358 - 财政年份:2014
- 资助金额:
$ 23.62万 - 项目类别:
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