一套用于对皮质细胞类型进行基因操控的增强子腺相关病毒（AAV）和转基因小鼠品系。

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

作者信息

Ben-Simon Yoav, Hooper Marcus, Narayan Sujatha, Daigle Tanya L, Dwivedi Deepanjali, Way Sharon W, Oster Aaron, Stafford David A, Mich John K, Taormina Michael J, Martinez Refugio A, Opitz-Araya Ximena, Roth Jada R, Alexander Jason R, Allen Shona, Amster Adam, Arbuckle Joel, Ayala Angela, Baker Pamela M, Bakken Trygve E, Barcelli Tyler, Barta Stuard, Bendrick Jacqueline, Bertagnolli Darren, Bielstein Cameron, Bishwakarma Prajal, Bowlus Jessica, Boyer Gabriella, Brouner Krissy, Casian Brittny, Casper Tamara, Chakka Anish B, Chakrabarty Rushil, Chance Rebecca K, Chavan Sakshi, Clark Michael, Colbert Kaity, Collman Forrest, Daniel Scott, Departee Maxwell, DiValentin Peter, Donadio Nicholas, Dotson Nadezhda, Egdorf Tom, Fliss Tim, Gabitto Mariano, Garcia Jazmin, Gary Amanda, Gasperini Molly, Gloe Jessica, Goldy Jeff, Gore Bryan B, Graybuck Lucas, Greisman Noah, Haeseleer Francoise, Halterman Carliana, Haradon Zeb, Hastings Samantha D, Helback Olivia, Ho Windy, Hockemeyer Dirk, Huang Cindy, Huff Sydney, Hunker Avery, Johansen Nelson, Jones Danielle, Juneau Zoe, Kalmbach Brian, Kannan Madhav, Khem Shannon, Kussick Emily, Kutsal Rana, Larsen Rachael, Lee Changkyu, Lee Angus Y, Leibly Madison, Lenz Garreck H, Li Su, Liang Elizabeth, Lusk Nicholas, Madigan Zachary, Malloy Jessica, Malone Jocelin, McCue Rachel, Melchor Jose, Mollenkopf Tyler, Moosman Skyler, Morin Elyse, Newman Dakota, Ng Lydia, Ngo Kiet, Omstead Victoria, Otto Sven, Oyama Alana, Pena Nick, Pham Trangthanh, Phillips Elliot, Pom Christina A, Potekhina Lydia, Ransford Shea, Ray Patrick L, Rette Dean, Reynoldson Cade, Rimorin Christine, Rocha Dana, Ruiz Augustin, Sanchez Raymond E A, Sawyer Lane, Sedeno-Cortes Adriana, Sevigny Joshua P, Shapovalova Nadiya, Shepard Noah, Shulga Lyudmila, Sigler Ana R, Siverts La'Akea, Soliman Sherif, Somasundaram Saroja, Staats Brian, Stewart Kaiya, Szelenyi Eric, Tieu Michael, Trader Cameron, Tran Alex, van Velthoven Cindy T J, Walker Miranda, Wang Yimin, Weed Natalie, Wirthlin Morgan, Wood Toren, Wynalda Brooke, Yao Zizhen, Zhou Thomas, Ariza Jeanelle, Dee Nick, Reding Melissa, Ronellenfitch Kara, Mufti Shoaib, Sunkin Susan M, Smith Kimberly A, Esposito Luke, Waters Jack, Thyagarajan Bargavi, Yao Shenqin, Lein Ed S, Zeng Hongkui, Levi Boaz P, Ngai John, Ting Jonathan T, Tasic Bosiljka

机构信息

Allen Institute for Brain Science, Seattle, WA 98109, USA.

University of California, Berkeley, Berkeley, CA 94720, USA.

出版信息

Cell. 2025 May 29;188(11):3045-3064.e23. doi: 10.1016/j.cell.2025.05.002. Epub 2025 May 21.

DOI:10.1016/j.cell.2025.05.002

PMID:40403729

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.

摘要

哺乳动物的皮层由根据共同特性分类的细胞组成。确定每种细胞类型对皮层所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。我们使用来自小鼠和人类的转录组学和表观基因组学皮层细胞类型分类法来定义标记基因和假定的增强子，并创建了一个大型转基因品系和增强子腺相关病毒（AAV）工具包，用于选择性靶向皮层细胞群体。我们报告了15个转基因驱动品系、2个报告品系以及超过1000种不同的增强子AAV载体的创建和评估，这些载体覆盖了皮层细胞的大多数亚类。这里报告的工具已公开可用，并且连同工具创建、评估和修改的规模化过程，它们将使人们能够采用多种实验策略来理解哺乳动物皮层和大脑功能。