小柯机器人

美国斯坦福大学医学院Michael T. Longaker 、Jeffrey A. Norton和Howard Y. Chang研究组通过多组学分析，揭示了跨物种和起源组织的肿瘤相关成纤维细胞(CAFs)表型的保守性。相关论文发表在2022年10月20日出版的《癌细胞》杂志上。

他们进一步用综合多组学方法探讨CAF异质性。使用成对的、同细胞染色质可及性和转录组分析，他们提供了一个复杂的空间转录组和蛋白质组景观上的CAF亚群的综合分析，以确定三个超簇：稳态样(SSL)、机械反应(MR)和免疫调节(IM) CAFs。这些超簇在多种组织类型和物种中重现。选择性破坏潜在的机械力或免疫检查点抑制治疗导致CAF亚群分布的变化并影响肿瘤生长。因此，CAF超簇之间的平衡可能具有相当大的转译意义。

总的来说，这项研究扩展了人们对CAF生物学的理解，确定了CAF分化的调控途径，并在物种和肿瘤未知情况下阐明了治疗靶点。

据悉，CAF是实体肿瘤微环境不可或缺的组成部分。CAF曾经被认为是一个相对统一的基质生产细胞群体，但单细胞RNA测序揭示了不同的CAF表型。

附：英文原文

Title: Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin

Author: Deshka S. Foster, Michael Januszyk, Daniel Delitto, Kathryn E. Yost, Michelle Griffin, Jason Guo, Nicholas Guardino, Andrea E. Delitto, Malini Chinta, Austin R. Burcham, Alan T. Nguyen, Khristian E. Bauer-Rowe, Ashley L. Titan, Ankit Salhotra, R. Ellen Jones, Oscar da Silva, Hunter G. Lindsay, Charlotte E. Berry, Kellen Chen, Dominic Henn, Shamik Mascharak, Heather E. Talbott, Alexia Kim, Fatemeh Nosrati, Dharshan Sivaraj, R. Chase Ransom, Michael Matthews, Anum Khan, Dhananjay Wagh, John Coller, Geoffrey C. Gurtner, Derrick C. Wan, Irene L. Wapnir, Howard Y. Chang, Jeffrey A. Norton, Michael T. Longaker

Issue&Volume: 2022-10-20

Abstract: Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment.CAFs were once thought to be a relatively uniform population of matrix-producing cells,but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we furtherprobed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cellchromatin accessibility and transcriptome analysis, we provided an integrated analysisof CAF subpopulations over a complex spatial transcriptomic and proteomic landscapeto identify three superclusters: steady state-like (SSL), mechanoresponsive (MR),and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multipletissue types and species. Selective disruption of underlying mechanical force or immunecheckpoint inhibition therapy results in shifts in CAF subpopulation distributionsand affected tumor growth. As such, the balance among CAF superclusters may have considerabletranslational implications. Collectively, this research expands our understandingof CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.

DOI: 10.1016/j.ccell.2022.09.015

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00444-5

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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