圣地亚哥科学研究所Juan Carlos Izpisua Belmonte研究小组报道了衰老和疾病中普遍存在的间充质漂移可通过部分重编程逆转。这一研究成果于2025年8月14日发表在国际顶尖学术期刊《细胞》上。

细胞和组织特性的丧失是衰老和许多疾病的标志，但其潜在机制尚不清楚。他们分析了来自40多种人体组织和20种疾病的基因表达数据，揭示了多种细胞类型间充质基因的普遍上调，以及基质细胞群组成的改变，这表明了“间充质漂移”（MD）。MD增加与疾病进展、患者生存率降低和死亡风险升高相关，而抑制关键MD转录因子可导致表观遗传返老还童。值得注意的是，Yamanaka因子诱导的部分重编程可以在去分化和获得多能性之前显著减少MD，在细胞和组织水平上使老化的转录组恢复活力。这些发现为部分重编程潜在的有益影响提供了机制见解，并为开发干预措施以逆转部分重编程方法的年龄相关疾病提供了框架。

附：英文原文

Title: Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming

Author: Jinlong Y. Lu, William B. Tu, Ronghui Li, Mingxi Weng, Bhargav D. Sanketi, Baolei Yuan, Pradeep Reddy, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

Issue&Volume: 2025-08-14

Abstract: The loss of cellular and tissue identity is a hallmark of aging and numerous diseases, but the underlying mechanisms are not well understood. Our analysis of gene expression data from over 40 human tissues and 20 diseases reveals a pervasive upregulation of mesenchymal genes across multiple cell types, along with an altered composition of stromal cell populations, denoting a “mesenchymal drift” (MD). Increased MD correlates with disease progression, reduced patient survival, and an elevated mortality risk, whereas suppression of key MD transcription factors leads to epigenetic rejuvenation. Notably, Yamanaka factor-induced partial reprogramming can markedly reduce MD before dedifferentiation and gain of pluripotency, rejuvenating the aging transcriptome at the cellular and tissue levels. These findings provide mechanistic insight into the underlying beneficial effects of partial reprogramming and offer a framework for developing interventions to reverse age-related diseases using the partial reprogramming approach.

DOI: 10.1016/j.cell.2025.07.031

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00853-0