美国麻省理工学院Tyler Jacks和哈佛大学Jason D. Buenrostro课题组合作取得一项新成果。他们发现表观基因组状态转换可用于表征小鼠肺腺癌肿瘤（LUAD）的进展。这一研究成果在线发表在2020年7月23日的《癌细胞》上。

研究人员鉴定了代表细胞身份丧失和向转移状态进展的表观基因组连续体。研究人员发现了这些细胞状态的共可及性调控程序，并推测了激活和抑制染色质的关键调节因子。在这些可及性程序中，研究确定了一个转移前的过渡，其特征为激活RUNX转录因子，该转录因子介导细胞外基质重塑以促进转移并可用于预测人类LUAD患者的生存率。

总之，这些结果证明了单细胞表观基因组学对于鉴定调控程序以揭示肿瘤进展机制和关键生物标志物的能力。

研究人员表示，维持细胞功能、细胞分化状态的调控网络在肿瘤发展过程中常常失调。

附：英文原文

Title: Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma

Author: Lindsay M. LaFave, Vinay K. Kartha, Sai Ma, Kevin Meli, Isabella Del Priore, Caleb Lareau, Santiago Naranjo, Peter M.K. Westcott, Fabiana M. Duarte, Venkat Sankar, Zachary Chiang, Alison Brack, Travis Law, Haley Hauck, Annalisa Okimoto, Aviv Regev, Jason D. Buenrostro, Tyler Jacks

Issue&Volume: 2020-07-23

Abstract: Regulatory networks that maintain functional, differentiated cell states are oftendysregulated in tumor development. Here, we use single-cell epigenomics to profilechromatin state transitions in a mouse model of lung adenocarcinoma (LUAD). We identifyan epigenomic continuum representing loss of cellular identity and progression towarda metastatic state. We define co-accessible regulatory programs and infer key activatingand repressive chromatin regulators of these cell states. Among these co-accessibilityprograms, we identify a pre-metastatic transition, characterized by activation ofRUNX transcription factors, which mediates extracellular matrix remodeling to promotemetastasis and is predictive of survival across human LUAD patients. Together, theseresults demonstrate the power of single-cell epigenomics to identify regulatory programsto uncover mechanisms and key biomarkers of tumor progression.

DOI: 10.1016/j.ccell.2020.06.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30310-X