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胰腺癌的单核和空间转录组分析确定了与新辅助治疗相关的多细胞动态变化
2022-07-31 10:51

美国麻省理工学院Aviv Regev,Tyler Jacks团队共同合作近期取得重要工作进展,他们通过胰腺癌的单核和空间转录组分析确定了与新辅助治疗相关的多细胞动态变化。这一研究成果2022年7月28日在线发表于《自然—遗传学》杂志上。

在这里,研究人员使用单核RNA测序和全转录组数字空间分析(DSP)对43个接受新辅助治疗或未接受治疗的原发性PDAC肿瘤标本,构建了构成PDAC的细胞亚型和空间群落的高分辨率分子景观。研究人员发现了恶性细胞和成纤维细胞中的重复表达程序,包括新发现的神经样祖细胞恶性细胞程序,该程序在化疗和放疗后富集,并且与独立队列中的不良预后相关。

整合空间和细胞谱显示了三个多细胞群落,其贡献来自恶性肿瘤、成纤维细胞和免疫亚型:经典、类鳞片状和治疗富集型。他们完善的分子和细胞分类学可以为临床试验中的分层提供一个框架,并作为针对特定细胞表型和多细胞相互作用的治疗靶向的路线图。

据介绍,胰腺导管腺癌(PDAC)是一种高致死性和难治性癌症。胰腺癌的分子分层仍处于初级阶段,尚未为临床管理或治疗开发提供信息。

附:英文原文

Title: Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment

Author: Hwang, William L., Jagadeesh, Karthik A., Guo, Jimmy A., Hoffman, Hannah I., Yadollahpour, Payman, Reeves, Jason W., Mohan, Rahul, Drokhlyansky, Eugene, Van Wittenberghe, Nicholas, Ashenberg, Orr, Farhi, Samouil L., Schapiro, Denis, Divakar, Prajan, Miller, Eric, Zollinger, Daniel R., Eng, George, Schenkel, Jason M., Su, Jennifer, Shiau, Carina, Yu, Patrick, Freed-Pastor, William A., Abbondanza, Domenic, Mehta, Arnav, Gould, Joshua, Lambden, Conner, Porter, Caroline B. M., Tsankov, Alexander, Dionne, Danielle, Waldman, Julia, Cuoco, Michael S., Nguyen, Lan, Delorey, Toni, Phillips, Devan, Barth, Jaimie L., Kem, Marina, Rodrigues, Clifton, Ciprani, Debora, Roldan, Jorge, Zelga, Piotr, Jorgji, Vjola, Chen, Jonathan H., Ely, Zackery, Zhao, Daniel, Fuhrman, Kit, Fropf, Robin, Beechem, Joseph M., Loeffler, Jay S., Ryan, David P., Weekes, Colin D., Ferrone, Cristina R., Qadan, Motaz, Aryee, Martin J., Jain, Rakesh K., Neuberg, Donna S., Wo, Jennifer Y., Hong, Theodore S., Xavier, Ramnik, Aguirre, Andrew J., Rozenblatt-Rosen, Orit, Mino-Kenudson, Mari, Castillo, Carlos Fernandez-del, Liss, Andrew S.

Issue&Volume: 2022-07-28

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions. Single-nucleus and spatial, whole-transcriptome profiling of 43 pancreatic adenocarcinomas provides a refined molecular and cellular classification, highlighting a new neoadjuvant treatment-associated neural-like progenitor tumor cell state.

DOI: 10.1038/s41588-022-01134-8

Source: https://www.nature.com/articles/s41588-022-01134-8

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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