دورية أكاديمية

AAVS1‐targeted, stable expression of ChR2 in human brain organoids for consistent optogenetic control

التفاصيل البيبلوغرافية
العنوان: AAVS1‐targeted, stable expression of ChR2 in human brain organoids for consistent optogenetic control
المؤلفون: Hong, Soojung, Lee, Juhee, Kim, Yunhee, Kim, Eunjee, Shin, Kunyoo
المساهمون: National Research Foundation of Korea, Samsung Science and Technology Foundation, Samsung
المصدر: Bioengineering & Translational Medicine ; ISSN 2380-6761 2380-6761
بيانات النشر: Wiley
سنة النشر: 2024
المجموعة: Wiley Online Library (Open Access Articles via Crossref)
الوصف: Self‐organizing brain organoids provide a promising tool for studying human development and disease. Here we created human forebrain organoids with stable and homogeneous expression of channelrhodopsin‐2 (ChR2) by generating AAVS1 safe harbor locus‐targeted, ChR2 knocked‐in human pluripotent stem cells (hPSCs), followed by the differentiation of these genetically engineered hPSCs into forebrain organoids. The resulting ChR2‐expressing human forebrain organoids showed homogeneous cellular expression of ChR2 throughout entire regions without any structural and functional perturbations and displayed consistent and robust neural activation upon light stimulation, allowing for the non‐virus mediated, spatiotemporal optogenetic control of neural activities. Furthermore, in the hybrid platform in which brain organoids are connected with spinal cord organoids and skeletal muscle spheroids, ChR2 knocked‐in forebrain organoids induced strong and consistent muscle contraction upon brain‐specific optogenetic stimulation. Our study thus provides a novel, non‐virus mediated, preclinical human organoid system for light‐inducible, consistent control of neural activities to study neural circuits and dynamics in normal and disease‐specific human brains as well as neural connections between brain and other peripheral tissues.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1002/btm2.10690
الإتاحة: https://doi.org/10.1002/btm2.10690Test
حقوق: http://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.1A8BB1EF
قاعدة البيانات: BASE