Cell Reports (Nov 2023)
An ultra-compact promoter drives widespread neuronal expression in mouse and monkey brains
- Jingyi Wang,
- Jianbang Lin,
- Yefei Chen,
- Jing Liu,
- Qiongping Zheng,
- Mao Deng,
- Ruiqi Wang,
- Yujing Zhang,
- Shijing Feng,
- Zhenyan Xu,
- Weiyi Ye,
- Yu Hu,
- Jiamei Duan,
- Yunping Lin,
- Ji Dai,
- Yu Chen,
- Yuantao Li,
- Tao Luo,
- Qian Chen,
- Zhonghua Lu
Affiliations
- Jingyi Wang
- Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen 518034, China; Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China
- Jianbang Lin
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China
- Yefei Chen
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Jing Liu
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Department of Anesthesiology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen 518027, China
- Qiongping Zheng
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Mao Deng
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China
- Ruiqi Wang
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Yujing Zhang
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shijing Feng
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Zhenyan Xu
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Weiyi Ye
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China
- Yu Hu
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Jiamei Duan
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
- Yunping Lin
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China
- Ji Dai
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Yu Chen
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Yuantao Li
- Department of Anesthesiology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen 518027, China; Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China
- Tao Luo
- Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen 518034, China
- Qian Chen
- University of Chinese Academy of Sciences, Beijing 100049, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Corresponding author
- Zhonghua Lu
- Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Biomedical Imaging Science and System Key Laboratory, Chinese Academy of Sciences, Shenzhen 518055, China; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 11
p. 113348
Abstract
Summary: Promoters are essential tools for basic and translational neuroscience research. An ideal promoter should possess the shortest possible DNA sequence with cell-type selectivity. However, whether ultra-compact promoters can offer neuron-specific expression is unclear. Here, we report the development of an extremely short promoter that enables selective gene expression in neurons, but not glial cells, in the brain. The promoter sequence originates from the human CALM1 gene and is only 120 bp in size. The CALM1 promoter (pCALM1) embedded in an adeno-associated virus (AAV) genome directed broad reporter expression in excitatory and inhibitory neurons in mouse and monkey brains. Moreover, pCALM1, when inserted into an all-in-one AAV vector expressing SpCas9 and sgRNA, drives constitutive and conditional in vivo gene editing in neurons and elicits functional alterations. These data demonstrate the ability of pCALM1 to conduct restricted neuronal gene expression, illustrating the feasibility of ultra-miniature promoters for targeting brain-cell subtypes.
