{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Giehrl-Schwab J"],"funding":["Helmholtz Association","Else Kröner-Fresenius-Stiftung","Chan Zuckerberg Initiative"],"pagination":["e14797"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9081909"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(5)"],"pubmed_abstract":["Direct reprogramming based on genetic factors resembles a promising strategy to replace lost cells in degenerative diseases such as Parkinson's disease. For this, we developed a knock-in mouse line carrying a dual dCas9 transactivator system (dCAM) allowing the conditional in vivo activation of endogenous genes. To enable a translational application, we additionally established an AAV-based strategy carrying intein-split-dCas9 in combination with activators (AAV-dCAS). Both approaches were successful in reprogramming striatal astrocytes into induced GABAergic neurons confirmed by single-cell transcriptome analysis of reprogrammed neurons in vivo. These GABAergic neurons functionally integrate into striatal circuits, alleviating voluntary motor behavior aspects in a 6-OHDA Parkinson's disea"],"journal":["EMBO molecular medicine"],"pubmed_title":["Parkinson's disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons."],"pmcid":["PMC9081909"],"funding_grant_id":["ZT‐I‐0007","2018/T20","xNet‐0041‐Phase2‐3"],"pubmed_authors":["Gotz M","Ibarra IL","Luecken MD","Holter SM","Koupourtidou C","Theis FJ","Ninkovic J","Wurst W","Masserdotti G","Truong DJ","Giesert F","Prakash N","Lao CL","Vogt Weisenhorn DM","Lefort S","Hembach S","Rauser B","Fischer-Sternjak J","Giehrl-Schwab J"],"additional_accession":[]},"is_claimable":false,"name":"Parkinson's disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons.","description":"Direct reprogramming based on genetic factors resembles a promising strategy to replace lost cells in degenerative diseases such as Parkinson's disease. For this, we developed a knock-in mouse line carrying a dual dCas9 transactivator system (dCAM) allowing the conditional in vivo activation of endogenous genes. To enable a translational application, we additionally established an AAV-based strategy carrying intein-split-dCas9 in combination with activators (AAV-dCAS). Both approaches were successful in reprogramming striatal astrocytes into induced GABAergic neurons confirmed by single-cell transcriptome analysis of reprogrammed neurons in vivo. These GABAergic neurons functionally integrate into striatal circuits, alleviating voluntary motor behavior aspects in a 6-OHDA Parkinson's disea","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-04T20:35:41.655Z","creation":"2025-02-19T03:58:46.186Z"},"accession":"S-EPMC9081909","cross_references":{"pubmed":["35373464"],"doi":["10.15252/emmm.202114797"]}}