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Series GSE149872 Query DataSets for GSE149872
Status Public on Mar 15, 2022
Title Rescuing voluntary motor behavior in a Parkinson´s disease model by aCRISPR mediated reprogramming of striatal astrocytes into induced GABAergic neurons
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cell replacement strategies of affected cells have been performed in clinical studies of Parkinson´s disease with variable outcome. Conversion of endogenous glial cells into functional neurons might represent a more reliable alternative, thus here we developed a knock-in mouse line carrying a dual dCas9 transactivator system (dCAM), which allowed the conditional activation of the endogenous genes Ascl1, Lmx1a, and Nr4a2 in striatal astrocytes in vivo by delivering sgRNAs specific for their endogenous loci. In order to move this successful approach toward translation, we established an AAV based activator system carrying intein-split-dCas9-VP64, SAM (AAV-dCAS) activators, and the specific sgRNAs targeting transcription factor combinations. Both systems, the dCAM and the AAV-dCAS approach were successful in reprogramming of striatal astrocytes into GABAergic neurons, which functionally integrate into striatal circuits as evidenced by the alleviation of specific motor behaviors in a 6-OHDA Parkinson’s disease model. Thus, the AAV-dCAS approach may enable clinical therapies for Parkinson´s disease by reprogramming striatal astrocytes.
Overall design Examination of cell composition and astrocyte to neuron reprogramming in murine striatal tissue.
Contributor(s) Giehrl-Schwab J, Giesert F, Rauser B, Lao C, Lefort S, Ibarra IL, Koupourtidou C, Luecken MD, Truong D, Fischer-Sternjak J, Ninkovic J, Hölter SM, Vogt Weisenhorn DM, Theis FJ, Götz M, Wurst W
Citation(s) 35373464
Submission date May 05, 2020
Last update date May 25, 2022
Contact name Wolfgang Wurst
Phone +498931874110
Organization name Helmholtz Zentrum München
Department Institute of Developmental Genetics
Street address Ingolstaedter Landstrasse 1
City Neuherberg
ZIP/Postal code 85764
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM4516243 Sample_MUC17744
GSM4516244 Sample_MUC17745
BioProject PRJNA630398
SRA SRP260062

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Supplementary file Size Download File type/resource
GSE149872_RAW.tar 13.2 Mb (http)(custom) TAR (of H5AD)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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