美国科罗拉多大学Justin Brumbaugh和Peter J. Dempsey课题组合作发现，H3K36甲基化调节肠上皮细胞的可塑性和再生能力。2025年1月8日，国际学术期刊《自然—细胞生物学》发表了这一成果。

研究人员使用小鼠小肠作为研究细胞可塑性的模型系统。研究发现，H3K36甲基化增强了细胞类型相关基因的表达，以维持肠上皮细胞的特化细胞身份。H3K36甲基化缺失会破坏细胞系的稳态并激活再生基因的表达。相应地，研究人员观察到在损伤诱导再生后，H3K36甲基化迅速发生可逆重塑。这些数据表明，H3K36甲基化在维持特化谱系、调节细胞可塑性和再生方面发挥重要作用。

据悉，细胞可塑性是发育和稳态过程所必需的，以便从干细胞和祖细胞分化为不同类型的细胞。分化后，特化细胞的可塑性必须受到限制，以保持组织的完整性和功能。因此，特化细胞的特性在平衡状态下是稳定的；然而，某些组织中的细胞会在损伤诱导的再生过程中恢复可塑性。虽然这些基因的表达受到严格调控，但限制或促进细胞可塑性的调控机制却鲜为人知。

附：英文原文

Title: H3K36 methylation regulates cell plasticity and regeneration in the intestinal epithelium

Author: Pashos, Alison R. S., Meyer, Anne R., Bussey-Sutton, Cameron, OConnor, Erin S., Coradin, Mariel, Coulombe, Marilyne, Riemondy, Kent A., Potlapelly, Sanjana, Strahl, Brian D., Hansson, Gunnar C., Dempsey, Peter J., Brumbaugh, Justin

Issue&Volume: 2025-01-08

Abstract: Plasticity is needed during development and homeostasis to generate diverse cell types from stem and progenitor cells. Following differentiation, plasticity must be restricted in specialized cells to maintain tissue integrity and function. For this reason, specialized cell identity is stable under homeostatic conditions; however, cells in some tissues regain plasticity during injury-induced regeneration. While precise gene expression controls these processes, the regulatory mechanisms that restrict or promote cell plasticity are poorly understood. Here we use the mouse small intestine as a model system to study cell plasticity. We find that H3K36 methylation reinforces expression of cell-type-associated genes to maintain specialized cell identity in intestinal epithelial cells. Depleting H3K36 methylation disrupts lineage commitment and activates regenerative gene expression. Correspondingly, we observe rapid and reversible remodelling of H3K36 methylation following injury-induced regeneration. These data suggest a fundamental role for H3K36 methylation in reinforcing specialized lineages and regulating cell plasticity and regeneration.

DOI: 10.1038/s41556-024-01580-y

Source: https://www.nature.com/articles/s41556-024-01580-y