Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species
Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species
Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have revealed substantial diversity of glial cells, particularly astrocytes. To better understand glial cell types and their roles in neurobiology, we built a new suite of adeno-associated viral (AAV)-based genetic tools to enable genetic access to astrocytes and oligodendrocytes. These oligodendrocyte and astrocyte enhancer-AAVs are highly specific (usually > 95% cell type specificity) with variable expression levels, and our astrocyte enhancer-AAVs show multiple distinct expression patterns reflecting the spatial distribution of astrocyte cell types. To provide the best glial-specific functional tools, several enhancer-AAVs were: optimized for higher expression levels, shown to be functional and specific in rat and macaque, shown to maintain specific activity in epilepsy where traditional promoters changed activity, and used to drive functional transgenes in astrocytes including Cre recombinase and acetylcholine-responsive sensor iAChSnFR. The astrocyte-specific iAChSnFR revealed a clear reward-dependent acetylcholine response in astrocytes of the nucleus accumbens during reinforcement learning. Together, this collection of glial enhancer-AAVs will enable characterization of astrocyte and oligodendrocyte populations and their roles across species, disease states, and behavioral epochs.
Mich John K.、Sunil Smrithi、Johansen Nelson、Martinez Refugio A.、Ben-Simon Yoav、Bishaw Yemeserach、Dee Nick、Ruiz Augustin、Sedeno-Cortes Adriana E.、Taskin Naz、Weed Natalie、Egdorf Tom、Groce Erin L.、Loftus Luke、Lusk Nicholas、Alice Pom Christina、Potekhina Lydia、Reding Melissa、Rimorin Christine、Valera Cuevas Nasmil J.、McMillen Delissa A.、Thyagarajan Bargavi、Podgorski Kaspar、Horwitz Gregory D.、Zeng Hongkui、Svoboda Karel、Oster Aaron、Gary Amanda、Opitz-Araya Ximena、Tieu Michael、Malone Jocelin、Leytze Mckaila、Gore Bryan B.、Hirschstein Daniel、Omstead Victoria、Kojima Yoshiko、Way Sharon W.、Yao Zizhen、Taormina Michael、Campos Jazmin、Ting Jonathan T.、Daigle Tanya L.、Yao Shenqin、Lein Ed S.、Mahoney Joseph T.、Shapovalova Nadiya V.、Goldy Jeff、Monet Deja、Kunst Michael、Casper Tamara、Canfield Ryan、Martin Naomi X.、Gibson Shane、Brouner Krissy、Waters Jack、Smith Kimberly A.、Levi Boaz P.、McGraw Medea、Tasic Bosiljka、Bakken Trygve
生物科学研究方法、生物科学研究技术分子生物学神经病学、精神病学
Mich John K.,Sunil Smrithi,Johansen Nelson,Martinez Refugio A.,Ben-Simon Yoav,Bishaw Yemeserach,Dee Nick,Ruiz Augustin,Sedeno-Cortes Adriana E.,Taskin Naz,Weed Natalie,Egdorf Tom,Groce Erin L.,Loftus Luke,Lusk Nicholas,Alice Pom Christina,Potekhina Lydia,Reding Melissa,Rimorin Christine,Valera Cuevas Nasmil J.,McMillen Delissa A.,Thyagarajan Bargavi,Podgorski Kaspar,Horwitz Gregory D.,Zeng Hongkui,Svoboda Karel,Oster Aaron,Gary Amanda,Opitz-Araya Ximena,Tieu Michael,Malone Jocelin,Leytze Mckaila,Gore Bryan B.,Hirschstein Daniel,Omstead Victoria,Kojima Yoshiko,Way Sharon W.,Yao Zizhen,Taormina Michael,Campos Jazmin,Ting Jonathan T.,Daigle Tanya L.,Yao Shenqin,Lein Ed S.,Mahoney Joseph T.,Shapovalova Nadiya V.,Goldy Jeff,Monet Deja,Kunst Michael,Casper Tamara,Canfield Ryan,Martin Naomi X.,Gibson Shane,Brouner Krissy,Waters Jack,Smith Kimberly A.,Levi Boaz P.,McGraw Medea,Tasic Bosiljka,Bakken Trygve.Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2023.09.20.558718.点此复制
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