小柯机器人

美国斯坦福大学医学院Thomas A. Rando研究组建立了death -seq，以识别细胞死亡和衰老疗法的调节因子。这一研究成果发表在近日出版的国际学术期刊《细胞—代谢》上。

他们建立了“death -seq”，这是一种优化的阳性选择CRISPR筛选，用于识别细胞死亡的增强子和机制。他们的筛选发现了已知的抗衰老ABT-263诱导的细胞死亡的协同增强子。该筛选还通过一种相关化合物ABT-199在年龄相关疾病模型中发现了细胞死亡和衰老细胞清除的诱导剂，ABT-199单独不具有衰老性，但毒性比ABT-263小。

death -seq能够系统筛选细胞死亡途径，揭示受调节的细胞死亡子程序的分子机制，并确定治疗各种病理状态(如衰老、癌症和纤维化)的药物靶点。

据悉，选择性消融受损细胞是一种不断发展的治疗衰老相关疾病的方法。由于细胞死亡的时间较短，而且难以对非分裂细胞进行检测，目前用于全基因组筛选的方法通常能力不足，无法确定哪些基因的缺失可能会促进受损或衰老细胞的死亡。

附：英文原文

Title: Death-seq identifies regulators of cell death and senolytic therapies

Author: Alex Colville, Jie-Yu Liu, Cristina Rodriguez-Mateo, Samantha Thomas, Heather D. Ishak, Ronghao Zhou, Julian D.D. Klein, David W. Morgens, Armon Goshayeshi, Jayesh S. Salvi, David Yao, Kaitlyn Spees, Scott J. Dixon, Chun Liu, June-Wha Rhee, Celine Lai, Joseph C. Wu, Michael C. Bassik, Thomas A. Rando

Issue&Volume:

Abstract: Selectively ablating damaged cells is an evolving therapeutic approach for age-relateddisease. Current methods for genome-wide screens to identify genes whose deletionmight promote the death of damaged or senescent cells are generally underpowered becauseof the short timescales of cell death as well as the difficulty of scaling non-dividingcells. Here, we establish “Death-seq,” a positive-selection CRISPR screen optimizedto identify enhancers and mechanisms of cell death. Our screens identified synergisticenhancers of cell death induced by the known senolytic ABT-263. The screen also identifiedinducers of cell death and senescent cell clearance in models of age-related diseasesby a related compound, ABT-199, which alone is not senolytic but exhibits less toxicitythan ABT-263. Death-seq enables the systematic screening of cell death pathways touncover molecular mechanisms of regulated cell death subroutines and identifies drugtargets for the treatment of diverse pathological states such as senescence, cancer,and fibrosis.

DOI: 10.1016/j.cmet.2023.08.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00303-0

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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