空间CRISPR基因组学识别了瘤微环境的调节者
Maxime Dhainaut1, Samuel A Rose2, Guray Akturk3
1Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Cell
|March 15, 2022
概括
我们开发了Perturb-map, 一种空间功能基因组学工具, Perturb-map显示,癌细胞中的TGFβ受体损失改变了瘤微环境和免疫细胞的存在.
科学领域:
- 基因组学
- 癌症生物学
- 免疫学
背景情况:
- 对于细胞内基因功能,CRISPR选是有效的,但对于细胞外和组织层面的分析是有限的.
- 在复杂的瘤微环境 (TME) 中理解基因功能对于癌症研究至关重要.
研究的目的:
- 开发和应用一种新的空间功能基因组学方法,Perturb-map,用于在组织环境中剖析细胞外基因功能.
- 在小鼠肺癌模型中研究基因淘汰对瘤生长,组织病理和免疫组成的影响.
主要方法:
- 开发一个空间功能基因组技术Perturb-map.
- 在小鼠肺癌模型中应用Perturb-map进行并行基因淘汰.
- 整合Perturb-map与空间转录组来进行CRISPR编辑瘤的综合分析.
主要成果:
- Perturb-map能够同时评估基因淘汰对瘤生长,组织病理和免疫细胞透的影响.
- 在Tgfbr2绝杀性瘤中,观察到纤维肌性TME表型与T细胞排除.
- 发现TGFβ信号和纤维细胞激活的升级,表明TGFβ生物可用性和免疫抑制增加.
结论:
- Perturb-map已被确立为组织中单细胞分辨功能基因组学的强大工具,同时保持空间结构.
- 癌细胞对TGFβ受体的反应显著影响TME,影响免疫细胞相互作用和瘤进展.
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