Cell-Cell Communication Analysis of Cancer Organoids Using Multimodal Single-Cell PTM and RNA Profiling

使用多模式单细胞 PTM 和 RNA 分析对癌症类器官进行细胞间通讯分析

• 批准号: MR/T028270/1
• 负责人: Christopher Tape
• 金额: $ 75.87万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT028270%2F1
• 关键词: Cell; Communication; Analysis; Cancer; Organoids

Studying how different cell-types collaborate is essential to our understanding of healthy tissues and diseases such as cancer. To investigate how tissues function, we need to measure both how signals are transferred between cells and how that information is processed within cells. Unfortunately, no technology currently exists to simultaneously measure signalling both within and between cells. We have previously developed a powerful technology to measure lots of signals within individual cell-types. Each of these signalling events describe how the cells are behaving - so being able to measure lots of them across different cells is extremely exciting. Unfortunately, our technology cannot measure communication signals between different cells. It has recently been shown that DNA-sequencing technologies can be adapted to study communication between cells. Unfortunately, these sequencing technologies cannot measure signals inside cells. The aim of this project is to develop a technology capable of measuring signalling both within and between single-cells in cancer. By integrating our existing single-cell signalling methods with new single-cell sequencing approaches, we will develop a 'multimodal' technology to study how different cell-types communicate in 'mini-organ' models of bowel cancer. Through understanding how different cells types collaborate to drive tumours, this work will provide novel therapeutic opportunities to treat bowel cancer.

研究不同类型的细胞如何协作对于我们理解健康组织和癌症等疾病至关重要。为了研究组织的功能，我们需要测量信号是如何在细胞之间传递的，以及这些信息是如何在细胞内处理的。不幸的是，目前还没有技术可以同时测量细胞内部和细胞之间的信号。我们之前已经开发了一种强大的技术来测量单个细胞类型内的大量信号。每一个信号事件都描述了细胞的行为，所以能够在不同的细胞中测量大量的信号事件是非常令人兴奋的。不幸的是，我们的技术无法测量不同细胞之间的通信信号。最近有研究表明，dna测序技术可以用于研究细胞间的通讯。不幸的是，这些测序技术不能测量细胞内的信号。该项目的目的是开发一种能够测量癌症单细胞内部和单细胞之间信号的技术。通过将我们现有的单细胞信号传导方法与新的单细胞测序方法相结合，我们将开发一种“多模式”技术来研究不同类型的细胞如何在肠癌的“微型器官”模型中进行交流。通过了解不同类型的细胞如何协同驱动肿瘤，这项工作将为治疗肠癌提供新的治疗机会。

项目成果

An oncogenic phenoscape of colonic stem cell polarization

• DOI: 10.1016/j.cell.2023.11.004
• 发表时间: 2023-12
• 期刊: Cell
• 影响因子: 64.5
• 作者: X. Qin;F. Cardoso Rodriguez;J. Sufi;P. Vlckova;Jeroen Claus;C. Tape

SIGNAL-seq: Multimodal Single-cell Inter- and Intra-cellular Signalling Analysis

• DOI: 10.1101/2024.02.23.581433
• 发表时间: 2024-03
• 期刊: bioRxiv
• 作者: James W. Opzoomer;Rhianna O’Sullivan;J. Sufi;R. Madsen;X. Qin;Ewa Basiarz;C. Tape

Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses

网格单细胞筛选揭示了患者源性类器官药物反应的基质调节

• DOI: 10.1101/2022.10.19.512668
• 发表时间: 2022
• 作者: Zapatero M

A Single-cell Perturbation Landscape of Colonic Stem Cell Polarisation

• DOI: 10.1101/2023.02.15.528008
• 发表时间: 2023-02
• 期刊: bioRxiv
• 作者: X. Qin;Ferran Cardoso Rodriguez;J. Sufi;P. Vlckova;J. Claus;C. Tape

Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses

• DOI: 10.1016/j.cell.2023.11.005
• 发表时间: 2023-12-07
• 期刊: CELL
• 影响因子: 64.5
• 作者: Zapatero，Maria Ramos;Tong，Alexander;Tape，Christopher J.
• 通讯作者: Tape，Christopher J.