NIDA Technology Development Initiative

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Enhancer viruses for combinatorial cell-subclass-specific labeling

Published in Neuron.

Authors: Lucas T Graybuck, Tanya L Daigle, Adriana E Sedeño-Cortés, Miranda Walker, Brian Kalmbach, Garreck H Lenz, Elyse Morin, Thuc Nghi Nguyen, Emma Garren, Jacqueline L Bendrick, Tae Kyung Kim, Thomas Zhou, Marty Mortrud, Shenqin Yao, La’ Akea Siverts, Rachael Larsen, Bryan B Gore, Eric R Szelenyi, Cameron Trader, Pooja Balaram, Cindy T J van Velthoven, Megan Chiang, John K Mich, Nick Dee, Jeff Goldy, Ali H Cetin, Kimberly Smith, Sharon W Way, Luke Esposito, Zizhen Yao, Viviana Gradinaru, Susan M Sunkin, Ed Lein, Boaz P Levi, Jonathan T Ting, Hongkui Zeng, Bosiljka Tasic

Paper presented by Dr. Katherine Savell and selected by the NIDA TDI Paper of the Month Committee

Publication Brief Description

The brain is comprised of multiple regions of heterogeneous cell types. Experimental access to distinct cell types is necessary to study normal function and disease states of the brain, and it is essential to determine if defined cell types are conserved between species. Two studies published last year harnessed single-cell chromatin accessibility to define and test cell-type-distinguishing enhancers for generating AAVs to express transgenes in discrete cell populations, and to study expression correspondence between species. These approaches provide researchers with one avenue to access specific cell types in the brain for targeted population studies and gene therapies.

Graybuck, Lucas T; Daigle, Tanya L; Sedeño-Cortés, Adriana E; Walker, Miranda; Kalmbach, Brian; Lenz, Garreck H; Morin, Elyse; Nguyen, Thuc Nghi; Garren, Emma; Bendrick, Jacqueline L; Kim, Tae Kyung; Zhou, Thomas; Mortrud, Marty; Yao, Shenqin; Siverts, La' Akea; Larsen, Rachael; Gore, Bryan B; Szelenyi, Eric R; Trader, Cameron; Balaram, Pooja; van Velthoven, Cindy T J; Chiang, Megan; Mich, John K; Dee, Nick; Goldy, Jeff; Cetin, Ali H; Smith, Kimberly; Way, Sharon W; Esposito, Luke; Yao, Zizhen; Gradinaru, Viviana; Sunkin, Susan M; Lein, Ed; Levi, Boaz P; Ting, Jonathan T; Zeng, Hongkui; Tasic, Bosiljka

Enhancer viruses for combinatorial cell-subclass-specific labeling Journal Article

In: Neuron, vol. 109, no. 9, pp. 1449–1464.e13, 2021, ISSN: 1097-4199.

Abstract | Links

@article{pmid33789083,

title = {Enhancer viruses for combinatorial cell-subclass-specific labeling},

author = {Lucas T Graybuck and Tanya L Daigle and Adriana E Sedeño-Cortés and Miranda Walker and Brian Kalmbach and Garreck H Lenz and Elyse Morin and Thuc Nghi Nguyen and Emma Garren and Jacqueline L Bendrick and Tae Kyung Kim and Thomas Zhou and Marty Mortrud and Shenqin Yao and La' Akea Siverts and Rachael Larsen and Bryan B Gore and Eric R Szelenyi and Cameron Trader and Pooja Balaram and Cindy T J van Velthoven and Megan Chiang and John K Mich and Nick Dee and Jeff Goldy and Ali H Cetin and Kimberly Smith and Sharon W Way and Luke Esposito and Zizhen Yao and Viviana Gradinaru and Susan M Sunkin and Ed Lein and Boaz P Levi and Jonathan T Ting and Hongkui Zeng and Bosiljka Tasic},

url = {https://pubmed.ncbi.nlm.nih.gov/33789083/},

doi = {10.1016/j.neuron.2021.03.011},

issn = {1097-4199},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Neuron},

volume = {109},

number = {9},

pages = {1449--1464.e13},

abstract = {Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells and identified enhancers specific for cell subclasses and types. When cloned into recombinant adeno-associated viruses (AAVs) and delivered to the brain, these enhancers drive transgene expression in specific cortical cell subclasses. We extensively characterized several enhancer AAVs to show that they label different projection neuron subclasses as well as a homologous neuron subclass in human cortical slices. We also show how coupling enhancer viruses expressing recombinases to a newly generated transgenic mouse, Ai213, enables strong labeling of three different neuronal classes/subclasses in the brain of a single transgenic animal. This approach combines unprecedented flexibility with specificity for investigation of cell types in the mouse brain and beyond.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}