小柯机器人

美国斯坦福大学医学院William J. Greenleaf、Michael P. Snyder等研究人员，合作利用单细胞分析确定息肉向结直肠癌恶性转化过程中细胞状态和组成的连续变化。该研究于2022年6月20日在线发表于国际一流学术期刊《自然—遗传学》。

为了绘制健康结肠到癌前腺瘤再到结直肠癌（CRC）转变过程中的细胞组成和细胞状态变化，研究人员从48个息肉、27个正常组织和6个CRC样品中收集了1000到10000个细胞的单细胞染色质可及性图谱和单细胞转录组，无论是否有生殖系APC突变。

很大一部分息肉和CRC细胞表现出类似干细胞的表型，研究人员定义了这些干细胞在从平衡状态发展到CRC时发生的一系列表观遗传和转录变化。晚期息肉含有越来越多的干细胞、调节性T细胞和一种癌前相关的纤维细胞亚型。在癌症状态下，研究人员观察到T细胞耗竭、RUNX1调控的癌症相关成纤维细胞以及与上皮细胞中HNF4A主题相关的可及性增加。散发性CRC中的DNA甲基化变化与沿此连续体的可及性变化强烈反相关，这进一步确定了息肉分子分期的调节标记。

附：英文原文

Title: Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer

Author: Becker, Winston R., Nevins, Stephanie A., Chen, Derek C., Chiu, Roxanne, Horning, Aaron M., Guha, Tuhin K., Laquindanum, Rozelle, Mills, Meredith, Chaib, Hassan, Ladabaum, Uri, Longacre, Teri, Shen, Jeanne, Esplin, Edward D., Kundaje, Anshul, Ford, James M., Curtis, Christina, Snyder, Michael P., Greenleaf, William J.

Issue&Volume: 2022-06-20

Abstract: To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps. Single-cell ATAC-seq and RNA-seq profiling traces the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC). A large proportion of polyp and CRC cells show a stem-like phenotype.

DOI: 10.1038/s41588-022-01088-x

Source: https://www.nature.com/articles/s41588-022-01088-x

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
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex