Decoding Spatially Resolved Single Cell Metabolic Trajectory of Tonsil Tissues and Organoids

解码扁桃体组织和类器官的空间分辨单细胞代谢轨迹

基本信息

  • 批准号:
    10751125
  • 负责人:
  • 金额:
    $ 19.68万
  • 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:
    2023-08-10 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Germinal centers (GCs) are the microstructural sites in secondary lymphoid organs that control B cell clonal expansion to produce high-affinity antibodies for achieving humoral immunity. GC structures are impaired in obstructive sleep apnea (OSA) patients, leading the deficiencies in immune responses in infected individuals. The role of B cell development through GC reactions has been well established. B-cell immunometabolism is crucial to meet the energy needs of rapid proliferation. OSA patients exhibited associations with metabolic syndrome and vulnerability to flu. However, the coordination of metabolic trajectories in B cells of OSA+ and OSA- patients is still not clearly understood. There is a critical need to decipher the B cell immunometabolism at the single cell level in GCs for identifying the metabolic defects in the immune system of OSA patients making them prone to life-threatening infections. Thus, this project will leverage the recently developed spatially resolved metabolic profiling framework (3D-SMF) to map B cell subsets and their metabolism in the tonsil tissues and organoids. Our long-term goal is to generate single cell metabolic insights of B cell development in GCs of OSA+ and OSA- patients in response to influenza. The goal of this project is to define spatially resolved B cell immunometabolism pixel-by-pixel in fixed human tissues and living tissues. We hypothesize that metabolic trajectories and spatial distributions of B-cell subsets will be defective in OSA+ compared to OSA- tissues and influenza response in OSA- tonsil-derived organoids will be more competent than OSA+ tonsil-derived organoids. The rationale for this hypothesis is based on the 3D-SMF data showing the depletion and enrichment of fatty acids in GCs located in native tonsil tissues and the recent evidence on OSA patients’ vulnerability to flu infections associated with metabolic syndrome. The central hypothesis will be tested by pursuing two specific Aims. Aim 1 will provide an integral understanding of the lipid-associated immunometabolism in B-cell subsets in human OSA+ and OSA- tonsil tissues (n=10 each) and engineered tonsil organoids. Aim 2 will define how the metabolic trajectory modeling of B cell subtypes differs in tonsil organoids exposed to influenza antigens in OSA+ and OSA- donors. To accomplish these Aims, 3D-SMF and multiplexed cytokine gene expression profiling will be used to analyze B cell immunometabolism through a pseudotime B cell development modeling and longitudinal metabolic trajectory comparisons of B cell subsets in biomaterial-based tonsil organoids. This project builds an interdisciplinary team integrating experts from spatial omics, biomaterials, pediatric OSA, and bioinformatics. The proposed application is innovative because it uses cutting-edge technology to define spatial metabolomics and proteomics of tonsil organoids and shifts from the traditional focus on T cell and B cell co-cultures, toward differences of B cell metabolism in physiologically relevant and dynamic OSA+ and OSA- tonsil organoids ex vivo. This research is significant because it defines B cell immunometabolism to understand why OSA patients are prone to flu infections.
生发中心(GCs)是次级淋巴器官中控制B细胞克隆的微结构部位

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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Ahmet F. Coskun其他文献

Clinically relevant clot resolution via a thromboinflammation-on-a-chip
通过芯片上血栓炎症实现临床相关的血栓溶解
  • DOI:
    10.1038/s41586-025-08804-7
  • 发表时间:
    2025-04-02
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Yongzhi Qiu;Jessica Lin;Audrey Wang;Zhou Fang;Yumiko Sakurai;Hyoann Choi;Evelyn K. Williams;Elaissa T. Hardy;Kristin Maher;Ahmet F. Coskun;Gary Woods;Wilbur A. Lam
  • 通讯作者:
    Wilbur A. Lam
A Dynamic Personalized Human 3D Organoid for the Study of the Tumor Microenvironment and Metabolism in Acute Myeloid Leukemia Using Patient-Derived Xenografts
  • DOI:
    10.1182/blood-2022-170225
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Alejandro De Janon;Madison Stout;Diana Fridlyand;Zhou Fang;Ahmet F. Coskun;Douglas K Graham;Athanasios Mantalaris;Deborah DeRyckere;Nicki Panoskaltsis
  • 通讯作者:
    Nicki Panoskaltsis
Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics
在生物材料、微流控和空间组学的交汇处解码衰老的衰老单细胞
  • DOI:
    10.1038/s41514-024-00178-w
  • 发表时间:
    2024-11-26
  • 期刊:
  • 影响因子:
    6.000
  • 作者:
    Abhijeet Venkataraman;Ivan Kordic;JiaXun Li;Nicholas Zhang;Nivik Sanjay Bharadwaj;Zhou Fang;Sandip Das;Ahmet F. Coskun
  • 通讯作者:
    Ahmet F. Coskun

Ahmet F. Coskun的其他文献

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{{ truncateString('Ahmet F. Coskun', 18)}}的其他基金

Dissecting subcellular and cellular organization by spatial molecular neighborhood networks
通过空间分子邻域网络剖析亚细胞和细胞组织
  • 批准号:
    10713565
  • 财政年份:
    2023
  • 资助金额:
    $ 19.68万
  • 项目类别:
Tissue systems biology of immune dysregulation in aging by single cell spatial metabolomics
通过单细胞空间代谢组学研究衰老过程中免疫失调的组织系统生物学
  • 批准号:
    10647249
  • 财政年份:
    2023
  • 资助金额:
    $ 19.68万
  • 项目类别:
Tracing spatial organization of germinal centers in rhesus macaques
追踪恒河猴生发中心的空间组织
  • 批准号:
    10762072
  • 财政年份:
    2023
  • 资助金额:
    $ 19.68万
  • 项目类别:
Spatial transcriptional phenotyping of Sjögren’s disease tissue-resident mesenchymal stromal cells and neighbors in labial salivary glands
干燥病组织驻留间充质基质细胞和唇唾液腺邻近细胞的空间转录表型
  • 批准号:
    10575107
  • 财政年份:
    2023
  • 资助金额:
    $ 19.68万
  • 项目类别:
Spatial Epigenomic Profiling of Immune Cell Signatures at Subcellular Resolution in Health and Disease
健康和疾病中免疫细胞特征的亚细胞分辨率空间表观基因组分析
  • 批准号:
    10065913
  • 财政年份:
    2018
  • 资助金额:
    $ 19.68万
  • 项目类别:
Spatial Epigenomic Profiling of Immune Cell Signatures at Subcellular Resolution in Health and Disease
健康和疾病中免疫细胞特征的亚细胞分辨率空间表观基因组分析
  • 批准号:
    10425357
  • 财政年份:
    2018
  • 资助金额:
    $ 19.68万
  • 项目类别:
Spatial Epigenomic Profiling of Immune Cell Signatures at Subcellular Resolution in Health and Disease
健康和疾病中免疫细胞特征的亚细胞分辨率空间表观基因组分析
  • 批准号:
    10201436
  • 财政年份:
    2018
  • 资助金额:
    $ 19.68万
  • 项目类别:

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