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

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

Yoav Ben-Simon  1 , Marcus Hooper  1 , Sujatha Narayan  1 , Tanya L Daigle  1 , Deepanjali Dwivedi  1 , Sharon W Way  1 , Aaron Oster  1 , David A Stafford  2 , John K Mich  1 , Michael J Taormina  1 , Refugio A Martinez  1 , Ximena Opitz-Araya  1 , Jada R Roth  1 , Jason R Alexander  1 , Shona Allen  2 , Adam Amster  1 , Joel Arbuckle  1 , Angela Ayala  1 , Pamela M Baker  1 , Trygve E Bakken  1 , Tyler Barcelli  1 , Stuard Barta  1 , Jacqueline Bendrick  1 , Darren Bertagnolli  1 , Cameron Bielstein  1 , Prajal Bishwakarma  1 , Jessica Bowlus  1 , Gabriella Boyer  1 , Krissy Brouner  1 , Brittny Casian  1 , Tamara Casper  1 , Anish B Chakka  1 , Rushil Chakrabarty  1 , Rebecca K Chance  2 , Sakshi Chavan  1 , Michael Clark  1 , Kaity Colbert  1 , Forrest Collman  1 , Scott Daniel  1 , Maxwell Departee  1 , Peter DiValentin  1 , Nicholas Donadio  1 , Nadezhda Dotson  1 , Tom Egdorf  1 , Tim Fliss  1 , Mariano Gabitto  1 , Jazmin Garcia  1 , Amanda Gary  1 , Molly Gasperini  1 , Jessica Gloe  1 , Jeff Goldy  1 , Bryan B Gore  1 , Lucas Graybuck  1 , Noah Greisman  1 , Francoise Haeseleer  1 , Carliana Halterman  1 , Zeb Haradon  1 , Samantha D Hastings  1 , Olivia Helback  1 , Windy Ho  1 , Dirk Hockemeyer  2 , Cindy Huang  1 , Sydney Huff  1 , Avery Hunker  1 , Nelson Johansen  1 , Danielle Jones  1 , Zoe Juneau  1 , Brian Kalmbach  1 , Madhav Kannan  1 , Shannon Khem  1 , Emily Kussick  1 , Rana Kutsal  1 , Rachael Larsen  1 , Changkyu Lee  1 , Angus Y Lee  2 , Madison Leibly  1 , Garreck H Lenz  1 , Su Li  1 , Elizabeth Liang  1 , Nicholas Lusk  1 , Zachary Madigan  1 , Jessica Malloy  1 , Jocelin Malone  1 , Rachel McCue  1 , Jose Melchor  1 , Tyler Mollenkopf  1 , Skyler Moosman  1 , Elyse Morin  1 , Dakota Newman  1 , Lydia Ng  1 , Kiet Ngo  1 , Victoria Omstead  1 , Sven Otto  1 , Alana Oyama  1 , Nick Pena  1 , Trangthanh Pham  1 , Elliot Phillips  1 , Christina A Pom  1 , Lydia Potekhina  1 , Shea Ransford  1 , Patrick L Ray  1 , Dean Rette  1 , Cade Reynoldson  1 , Christine Rimorin  1 , Dana Rocha  1 , Augustin Ruiz  1 , Raymond E A Sanchez  1 , Lane Sawyer  1 , Adriana Sedeno-Cortes  1 , Joshua P Sevigny  1 , Nadiya Shapovalova  1 , Noah Shepard  1 , Lyudmila Shulga  1 , Ana R Sigler  1 , La'Akea Siverts  1 , Sherif Soliman  1 , Saroja Somasundaram  1 , Brian Staats  1 , Kaiya Stewart  1 , Eric Szelenyi  1 , Michael Tieu  1 , Cameron Trader  1 , Alex Tran  1 , Cindy T J van Velthoven  1 , Miranda Walker  1 , Yimin Wang  1 , Natalie Weed  1 , Morgan Wirthlin  1 , Toren Wood  1 , Brooke Wynalda  1 , Zizhen Yao  1 , Thomas Zhou  1 , Jeanelle Ariza  1 , Nick Dee  1 , Melissa Reding  1 , Kara Ronellenfitch  1 , Shoaib Mufti  1 , Susan M Sunkin  1 , Kimberly A Smith  1 , Luke Esposito  1 , Jack Waters  1 , Bargavi Thyagarajan  1 , Shenqin Yao  1 , Ed S Lein  1 , Hongkui Zeng  1 , Boaz P Levi  1 , John Ngai  2 , Jonathan T Ting  1 , Bosiljka Tasic  3
Affiliations
Free article

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

Yoav Ben-Simon et al. Cell. .
Free article

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.

Keywords: AAV; cell type; enhancer; epigenetics; human; mouse; neocortex; recombinase; transcriptomics; transgenic.

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Conflict of interest statement

Declaration of interests H.Z. is on the scientific advisory board of MapLight Therapeutics, Inc. The Allen Institute for Brain Science has filed patent applications for many enhancer AAVs described in this manuscript with multiple authors listed as inventors. B.P.L., B.B.G., J.K.M., and E.S.L. are founders of EpiCure Therapeutics, Inc.

Update of

  • A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.
    Ben-Simon Y, Hooper M, Narayan S, Daigle T, Dwivedi D, Way SW, Oster A, Stafford DA, Mich JK, Taormina MJ, Martinez RA, Opitz-Araya X, Roth JR, Allen S, Ayala A, Bakken TE, Barcelli T, Barta S, Bendrick J, Bertagnolli D, Bowlus J, Boyer G, Brouner K, Casian B, Casper T, Chakka AB, Chakrabarty R, Chance RK, Chavan S, Departee M, Donadio N, Dotson N, Egdorf T, Gabitto M, Garcia J, Gary A, Gasperini M, Goldy J, Gore BB, Graybuck L, Greisman N, Haeseleer F, Halterman C, Helback O, Hockemeyer D, Huang C, Huff S, Hunker A, Johansen N, Juneau Z, Kalmbach B, Khem S, Kussick E, Kutsal R, Larsen R, Lee C, Lee AY, Leibly M, Lenz GH, Liang E, Lusk N, Malone J, Mollenkopf T, Morin E, Newman D, Ng L, Ngo K, Omstead V, Oyama A, Pham T, Pom CA, Potekhina L, Ransford S, Rette D, Rimorin C, Rocha D, Ruiz A, Sanchez REA, Sedeno-Cortes A, Sevigny JP, Shapovalova N, Shulga L, Sigler AR, Siverts LA, Somasundaram S, Stewart K, Szelenyi E, Tieu M, Trader C, van Velthoven CTJ, Walker M, Weed N, Wirthlin M, Wood T, Wynalda B, Yao Z, Zhou T, Ariza J, Dee N, Reding M, Ronellenfitch K, Mufti S, Sunkin SM, Smith KA, Esposito L, Waters J, Thyagarajan B, Yao S, Lein ES, Zeng H, Levi BP, Ngai J, Ting J, Tasic B. Ben-Simon Y, et al. bioRxiv [Preprint]. 2024 Sep 26:2024.06.10.597244. doi: 10.1101/2024.06.10.597244. bioRxiv. 2024. Update in: Cell. 2025 May 29;188(11):3045-3064.e23. doi: 10.1016/j.cell.2025.05.002. PMID: 38915722 Free PMC article. Updated. Preprint.

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