哈佛大学Jason D. Buenrostro团队宣布他们的最新研究探明了结肠炎的表观遗传记忆促进肿瘤生长。该研究于2026年3月25日发表于国际一流学术期刊《自然》杂志上。

使用结肠炎的单主题模型，该课题组研究人员证明结肠干细胞在疾病消退后保留炎症的表观遗传记忆，持续超过100天。

在这里，课题组人员发现结肠炎的记忆以激活蛋白1（AP-1）转录因子活性的累积增益为特征，并伴随染色质可及性的持久变化。此外，研究组还开发了SHARE-TRACE方法，该方法可以同时分析单细胞中的基因表达、染色质可及性和克隆历史，从而实现高分辨率的表观基因组记忆跟踪。这种方法揭示了结肠炎的记忆是细胞内在的传播，并通过干细胞分裂遗传，一些克隆比其他克隆表现出更强的记忆。

最后，该课题组人员发现结肠炎诱导干细胞在致癌突变后增加AP-1调控基因程序的表达，从而加速肿瘤生长，这是一种依赖于AP-1活性的表型。总之，他们的发现提供了慢性炎症和恶性肿瘤之间的机制联系，揭示了再生组织中长期存在的表观遗传改变如何有助于疾病易感性，并提出了潜在的诊断和治疗策略，以减轻慢性炎症患者的癌症风险。

研究人员表示，慢性炎症是一个公认的癌症危险因素，但其潜在的分子机制尚不清楚。

附：英文原文

Title: Epigenetic memory of colitis promotes tumour growth

Author: Nagaraja, Surya, Ojeda-Miron, Lety, Zhang, Ruochi, Oreskovic, Ena, Hock, Conrad, Hu, Yan, Zeve, Daniel, Sharma, Karina, Hyman, Roni R., Zhang, Qiming, Castillo, Andrew, Breault, David T., Yilmaz, mer H., Buenrostro, Jason D.

Issue&Volume: 2026-03-25

Abstract: Chronic inflammation is a well-established risk factor for cancer, but the underlying molecular mechanisms remain unclear1,2. Using a mouse model of colitis, we demonstrate that colonic stem cells retain an epigenetic memory of inflammation following disease resolution that persists for more than 100days. Here we find that memory of colitis is characterized by a cumulative gain of activator protein 1 (AP-1) transcription factor activity, with durable changes to chromatin accessibility. Further, we develop SHARE-TRACE, a method that enables simultaneous profiling of gene expression, chromatin accessibility and clonal history in single cells, enabling high-resolution tracking of epigenomic memory. This approach reveals that memory of colitis is propagated cell-intrinsically and inherited through stem cell divisions, with some clones demonstrating stronger memory than others. Finally, we show that colitis primes stem cells for increased expression of an AP-1-regulated gene program following oncogenic mutation that accelerates tumour growth, a phenotype dependent on AP-1 activity. Together, our findings provide a mechanistic link between chronic inflammation and malignancy, revealing how long-lived epigenetic alterations in regenerative tissues may contribute to disease susceptibility and suggesting potential diagnostic and therapeutic strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

DOI: 10.1038/s41586-026-10258-4

Source: https://www.nature.com/articles/s41586-026-10258-4