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

作者：Yoav Ben‐Simon, Marcus Hooper, Sujatha Narayan, Tanya L. Daigle, Deepanjali Dwivedi, Sharon W. Way, Aaron Oster, David Stafford, John K. Mich, Michael J. Taormina, Refugio A. Martinez, Ximena Opitz-Araya, J. Roth, Jason R. Alexander, Shona W. Allen, Adam Amster, Joel Arbuckle, Angela Ayala, Pamela Baker, Trygve E. Bakken, Tyler Barcelli, Stuard Barta, Jacqueline L. Bendrick, Darren Bertagnolli, Cameron Bielstein, Prajal Bishwakarma, Jessica Bowlus, Gabriella Boyer, Krissy Brouner, Brittny Casian, Tamara Casper, Anish Bhaswanth 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 I. Gabitto, Jazmin Garcia, Amanda Gary, Molly Gasperini, Jessica Gloe, Jeff Goldy, Bryan B. Gore, Lucas T. Graybuck, Noah Greisman, Françoise Haeseleer, Carliana Halterman, Zeb Haradon, Samantha D. Hastings, Olivia Helback, Windy Ho, Dirk Hockemeyer, Cindy Huang, Sydney Huff, Avery C. Hunker, Nelson Johansen, Danielle Jones, Zoe Juneau, Brian Kalmbach, Madhav Kannan, Shannon Khem, Emily Kussick, Rana Kutsal, Rachael Larsen, Changkyu Lee, Angus Y. Lee, Madison Leibly, Garreck Lenz, Li Su, Elizabeth Liang, Nicholas A. Lusk, Zachary Madigan, Jessica Malloy, Jocelin Malone, Rachel McCue, Jose Melchor, Tyler Mollenkopf, Skyler Moosman, Elyse L. Morin, Dakota Newman, Lydia Ng, Kiet Ngo, Victoria Omstead, Sven Otto, Alana Oyama, Nick Pena, Trangthanh Pham, Elliot J Phillips, Christina Alice Pom, Lydia Potekhina, Shea Ransford, Patrick L. Ray, Dean F. Rette, Cade Reynoldson, Christine Rimorin, Dana B. Rocha, Augustin Ruiz, Raymond Sanchez, Lane Sawyer, Adriana E. Sedeño-Cortés, Joshua P Sevigny, Nadiya V. Shapovalova, Noah Shepard, Lyudmila Shulga, Ana Rios Sigler, La’Akea Siverts, Sherif Soliman, Saroja Somasundaram, Brian Staats, K.J. Stewart, Eric R Szelenyi, Michael Tieu, Cameron Trader, Alex Tran, Cindy T. J. van Velthoven, Miranda Walker, Yimin Wang, Natalie Weed, Morgan Wirthlin, Toren Wood, Brooke Wynalda, Zizhen Yao, Tingfa Zhou, Jeanelle Ariza, Nick Dee, Melissa Reding, Kara Ronellenfitch, Shoaib Mufti, Susan M. Sunkin, Kimberly A. Smith, Luke Esposito, Jack Waters, Bargavi Thyagarajan, Shenqin Yao, Ed S. Lein, Hongkui Zeng, Boaz P. Levi, John Ngai, Jonathan T. Ting, Bosiljka Tasic · 发表于：Cell · 年份：2025 · DOI：10.1016/j.cell.2025.05.002 · 被引用次数：57 · 研究领域：CRISPR and Genetic Engineering、Single-cell and spatial transcriptomics、Virus-based gene therapy research

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.