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Series GSE273504 Query DataSets for GSE273504
Status Public on Jul 31, 2024
Title Engineered T cell therapy for central nervous system injury [CSF RNAseq + VDJ]
Organism Homo sapiens
Experiment type Other
Summary Traumatic injuries to the central nervous system (CNS) affect millions of people worldwide yet lack an effective treatment. These injuries contain infiltrating immune cells that can promote tissue repair and could be exploited for therapeutic benefit. Here, using single-cell RNA-sequencing of T cells infiltrating the injured CNS we demonstrate their clonal expansion and antigen specificity towards CNS derived self-peptides. We confirm the beneficial effect of these injury-associated autoimmune CD4+ T cells in murine models of optic nerve and spinal cord injury. Subsequently, using mRNA-based transient T cell receptor (TCR) reconstitution, we demonstrate a therapeutic T cell strategy to alleviate CNS injury. Treatment of CNS-injured mice with this therapy improved locomotion and alleviated histological signs of damage, through regulation of myeloid cells, without detrimental autoimmune side effects. This strategy provides a means of developing custom-designed T cell therapies for CNS injury, and possibly for other neurodegenerative disorders.
 
Overall design Human CSF was collected via a lumbar drain daily from SCI patients. 10 mL of CSF was used at each time point for cell isolation. CSF was transferred into a 15 mL centrifuge tube and centrifuged at 500 g for 5 minutes. The supernatant was removed and cell pellet was resuspended with PBS containing 0.04 % BSA and filtered with 40 μm cell strainer. Cell number and viability were determined using Viastain AOPI Staining Solution (CS2-0106, Nexcelom Bioscience) and the CellDrop FL Fluorescence Cell Counter (DeNovix). Cell samples were loaded onto a 10X Genomics Chromium platform for Gel Bead-in Emulsions (GEMs) and Human T cell Chromium Single Cell V(D)J Enrichment Kit and Chromium Single Cell 5’ Library & Gel Bead Kit were used separately to generate a cDNA library targeting the TCR and for transcriptome expression.
Web link https://www.nature.com/articles/s41586-024-07906-y
 
Contributor(s) Gao W, Dykstra T, Kipnis J
Citation(s) 39232158
Submission date Jul 30, 2024
Last update date Oct 22, 2024
Contact name Jonathan Kipnis
Organization name Washington University in Saint Louis
Department Pathology and Immunology
Lab Kipnis Lab
Street address 4515 McKinley Ave
City Saint Louis
State/province MO
ZIP/Postal code 63110
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (24)
GSM8430297 RNA-Seq P1.Day1
GSM8430298 RNA-Seq P1.Day3
GSM8430299 RNA-Seq P1.Day5
This SubSeries is part of SuperSeries:
GSE216391 Engineered T cell therapy for central nervous system injury
Relations
BioProject PRJNA1142026

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE273504_P1.Day1.tar.gz 15.1 Mb (ftp)(http) TAR
GSE273504_P1.Day1_filteredcontig.tar.gz 140.1 Kb (ftp)(http) TAR
GSE273504_P1.Day3.tar.gz 42.7 Mb (ftp)(http) TAR
GSE273504_P1.Day3_filteredcontig.tar.gz 640.5 Kb (ftp)(http) TAR
GSE273504_P1.Day5.tar.gz 21.1 Mb (ftp)(http) TAR
GSE273504_P1.Day5_filteredcontig.tar.gz 449.4 Kb (ftp)(http) TAR
GSE273504_P2.Day3.tar.gz 38.5 Mb (ftp)(http) TAR
GSE273504_P2.Day3_filteredcontig.tar.gz 1.3 Mb (ftp)(http) TAR
GSE273504_P2.Day5.tar.gz 23.4 Mb (ftp)(http) TAR
GSE273504_P2.Day5_filteredcontig.tar.gz 987.7 Kb (ftp)(http) TAR
GSE273504_P3.Day5.tar.gz 53.9 Mb (ftp)(http) TAR
GSE273504_P3.Day5_filteredcontig.tar.gz 1.2 Mb (ftp)(http) TAR
GSE273504_P4.Day1.tar.gz 72.8 Mb (ftp)(http) TAR
GSE273504_P4.Day1_filteredcontig.tar.gz 2.4 Mb (ftp)(http) TAR
GSE273504_P4.Day3.tar.gz 113.6 Mb (ftp)(http) TAR
GSE273504_P4.Day3_filteredcontig.tar.gz 3.5 Mb (ftp)(http) TAR
GSE273504_P4.Day5.tar.gz 115.4 Mb (ftp)(http) TAR
GSE273504_P4.Day5_filteredcontig.tar.gz 2.7 Mb (ftp)(http) TAR
GSE273504_P5.Day1.tar.gz 105.7 Mb (ftp)(http) TAR
GSE273504_P5.Day1_filteredcontig.tar.gz 743.0 Kb (ftp)(http) TAR
GSE273504_P5.Day3.tar.gz 48.1 Mb (ftp)(http) TAR
GSE273504_P5.Day3_filteredcontig.tar.gz 950.1 Kb (ftp)(http) TAR
GSE273504_P5.Day5.tar.gz 79.6 Mb (ftp)(http) TAR
GSE273504_P5.Day5_filteredcontig.tar.gz 1.2 Mb (ftp)(http) TAR
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