美国艾伦脑科学研究所Angus Y. Lee小组揭示了一套增强子AAV和转基因小鼠系用于皮质细胞类型的遗传通路。该研究于2025年5月21日发表于国际一流学术期刊《细胞》杂志上。

该课题组人员将来自motheme和人类的皮质细胞类型转录组和表观基因组分类定义为标记基因和假定的增强子，并创建了一个大型的转基因系和增强子腺相关病毒主题（AAVs）工具箱，用于选择性靶向皮质细胞群体。该课题组报告了15个转基因驱动系、2个报告系和1000个不同的AAV增强子载体的创建和评估，涵盖了大多数皮层细胞亚类。这里报告的工具已经公开可用，并且随着工具创建，评估和修改的规模化过程，它们将使理解哺乳动物皮层和大脑功能的实验策略多样化。

研究人员表示，哺乳动物的皮层是由不同类型的细胞组成的。定义每一种细胞类型对由皮层引导的过程的贡献对于理解其在健康和疾病中的功能至关重要。

附：英文原文

Title: A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types

Author: Yoav Ben-Simon, Marcus Hooper, Sujatha Narayan, Tanya L. Daigle, Deepanjali Dwivedi, Sharon W. Way, Aaron Oster, David A. Stafford, John K. Mich, Michael J. Taormina, Refugio A. Martinez, Ximena Opitz-Araya, Jada R. Roth, Jason R. Alexander, Shona Allen, Adam Amster, Joel Arbuckle, Angela Ayala, Pamela M. Baker, Trygve E. Bakken, Tyler Barcelli, Stuard Barta, Jacqueline Bendrick, Darren Bertagnolli, Cameron Bielstein, Prajal Bishwakarma, Jessica Bowlus, Gabriella Boyer, Krissy Brouner, Brittny Casian, Tamara Casper, Anish B. Chakka, Rushil Chakrabarty, Rebecca K. Chance, Sakshi Chavan, Michael Clark, Kaity Colbert, Forrest Collman, Scott Daniel, Maxwell Departee, Peter DiValentin, Nicholas Donadio, Nadezhda Dotson, Tom Egdorf, Tim Fliss, Mariano Gabitto, Jazmin Garcia, Amanda Gary, Molly Gasperini, Jessica Gloe, Jeff Goldy, Bryan B. Gore, Lucas Graybuck, Noah Greisman, Francoise Haeseleer, Carliana Halterman, Zeb Haradon, Samantha D. Hastings, Olivia Helback, Windy Ho, Dirk Hockemeyer, Cindy Huang, Sydney Huff, Avery Hunker, Nelson Johansen, Danielle Jones, Zoe Juneau, Brian Kalmbach, Madhav Kannan, Shannon Khem, Emily Kussick, Rana Kutsal, Rachael Larsen, Changkyu Lee, Angus Y. Lee

Issue&Volume: 2025-05-21

Abstract: The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We use transcriptomic and epigenomic cortical cell-type taxonomies from mouse and human to define marker genes and putative enhancers and create a large toolkit of transgenic lines and enhancer adeno-associated viruses (AAVs) for selective targeting of cortical cell populations. We report creation and evaluation of fifteen transgenic driver lines, two reporter lines, and >1,000 different enhancer AAV vectors covering most subclasses of cortical cells. The tools reported here have been made publicly available, and along with the scaled process of tool creation, evaluation, and modification, they will enable diverse experimental strategies toward understanding mammalian cortex and brain function.

DOI: 10.1016/j.cell.2025.05.002

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00513-6