التفاصيل البيبلوغرافية
| العنوان: |
Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex |
| المؤلفون: |
Mich, John K., Graybuck, Lucas T., Hess, Erik E., Mahoney, Joseph T., Kojimo, Yoshiko, Ding, Yi, Somasundaram, Saroja, Miller, Jeremy A., Kalmbach, Brian E., Radaelli, Cristina, Gore, Bryan B., Weed, Natalie, Omstead, Victoria, Bishaw, Yemeserach, Shapovalova, Nadiya V., Martinez, Refugio A., Fong, Olivia, Yao, Shenqin, Mortrud, Marty, Chong, Peter, Loftus, Luke, Bertagnolli, Darren, Goldy, Jeff, Casper, Tamara, Dee, Nick, Opitz-Araya, Ximena, Cetin, Ali, Smith, Kimberly A., Gwinn, Ryder P., Cobbs, Charles, Ko, Andrew L., Ojemann, Jeffrey G., Keene, C. Dirk, Silbergeld, Daniel L., Sunkin, Susan M., Gradinaru, Viviana, Horwitz, Gregory D., Zeng, Hongkui, Tasic, Bosiljka, Lein, Ed S., Ting, Jonathan T., Levi, Boaz P. |
| المصدر: |
Cell Reports, 34(13), Art. No. 108754, (2021-03-30) |
| بيانات النشر: |
Elsevier |
| سنة النشر: |
2021 |
| المجموعة: |
Caltech Authors (California Institute of Technology) |
| مصطلحات موضوعية: |
human, macaque, brain cell types, epigenetics, enhancers, AAVs, genetic tools, ex vivo brain slice, ATAC-seq, parvalbumin |
| الوصف: |
Viral genetic tools that target specific brain cell types could transform basic neuroscience and targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome to control gene expression in adeno-associated virus (AAV) vectors. The cellular specificity of reporter expression from enhancer-AAVs is established by molecular profiling after systemic AAV delivery in mouse. Over 30% of enhancer-AAVs produce specific expression in the targeted subclass, including both excitatory and inhibitory subclasses. We present a collection of Parvalbumin (PVALB) enhancer-AAVs that show highly enriched expression not only in cortical PVALB cells but also in some subcortical PVALB populations. Five vectors maintain PVALB-enriched expression in primate neocortex. These results demonstrate how genome-wide open chromatin data mining and cross-species AAV validation can be used to create the next generation of non-species-restricted viral genetic tools. ; © 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/). Received 14 April 2020, Revised 7 July 2020, Accepted 25 January 2021, Available online 30 March 2021. We thank Allison Beller, Nathan Hansen, Caryl Tongco, Jae-Guen Yoon, and Gina DeNoble for assistance with obtaining patient consent and human neurosurgical tissue research specimens. We thank Rebecca D. Hodge, Trygve E. Bakken, and Zizhen Yao for assistance with sc/snRNA-seq data. We thank Lisa McConnell for assisting with NHP virus injection surgery and NHP animal care. We thank Allen Institute Tissue Procurement and Facilities teams for institutional support during tissue collections. In addition, we wish to thank the Allen Institute for Brain Science founder, Paul G. Allen, for his vision, encouragement, and support. This work is supported by NIH BRAIN Initiative award 1RF1MH114126-01 from the National Institute of Mental Health to ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://doi.org/10.1101/555318Test; https://doi.org/10.1016/j.celrep.2021.108754Test; oai:authors.library.caltech.edu:twtz6-z9n14; eprintid:102694; resolverid:CaltechAUTHORS:20200421-093728277 |
| DOI: |
10.1016/j.celrep.2021.108754 |
| الإتاحة: |
https://doi.org/10.1016/j.celrep.2021.10875410.1101/555318Test |
| حقوق: |
info:eu-repo/semantics/openAccess ; Other |
| رقم الانضمام: |
edsbas.E8EC2A67 |
| قاعدة البيانات: |
BASE |
