在外分泌胰腺疾病中发现了新型的状转化性状态
Katherine J Aney1, Woo-Jeong Jeong2, Pal Koak2
1Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA; Health Sciences & Technology Program, Harvard-MIT, Boston, MA 02115, USA; Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Cellular and molecular gastroenterology and hepatology
|December 26, 2025
概括
在受伤时,胰腺的状细胞会改变身份,这可能导致癌症. 这项研究揭示了不同疾病中这些变化背后的共同细胞程序,识别了早期癌症亚型的特征.
科学领域:
- 在胰腺疾病中细胞可塑性和转化.
背景情况:
- 胰腺酸性至导管性转化症 (ADM) 是对损伤的细胞反应,可以解决或导致胰腺癌.
- 不同的胰腺压力因素所驱动的特定的代塑性程序尚未完全理解.
研究的目的:
- 在各种疾病模型中全面定义外分胰腺的转化性反应.
- 要了解多种胰腺压力因素是否会诱导一种共享或独特的膜至导管性转化症 (ADM) 程序.
主要方法:
- 来自急性,复发性和慢性胰腺炎的小鼠模型中的超过30万个细胞的单细胞转录基因分析,以及瘤性Kras.
- 利用FixNCut方法在富含酶的胰腺组织中获得高质量的RNA完整性.
- 在人类胰腺组织中使用CosMx空间转录学验证的发现.
主要成果:
- 确定了一种保存的酸性反应,产生了独特的元塑性状态,包括一个"门户"ADM群体.
- 在胰腺内皮质瘤 (PanIN) 病变中检测到古典类和基底类状态,表明早期癌症亚型的特征.
- 在PanIN形成期间,在Kras-mutant组织中观察到第二波炎症和免疫抑制.
结论:
- 在异位胰腺疾病中定义了一种保存的acinar可塑性程序.
- 在前体病变形成期间,未解决的ADM与免疫重塑有关.
- 在早期的PanIN病变中观察到胰腺癌亚型的出现.
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