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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 02, 2024 |
| Title |
Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
After a stroke, the neurogenic response from the subventricular zone (SVZ) to repair the brain is limited. Microglia, as an integral part of the distinctive SVZ microenvironment, control neural stem / precursor cell (NSPC) behavior. Here, we show that discrete stroke-associated SVZ microglial clusters negatively impact the innate neurogenic response, and we propose a repository of relevant microglia–NSPC ligand–receptor pairs. After photothrombosis, a mouse model of ischemic stroke, the altered SVZ niche environment leads to immediate activation of microglia in the niche and an abnormal neurogenic response, with cell-cycle arrest of neural stem cells and neuroblast cell death. Pharmacological restoration of the niche environment increases the SVZ-derived neurogenic repair and microglial depletion increases the formation and survival of newborn neuroblasts in the SVZ. Therefore, we propose that altered cross-communication between microglial subclusters and NSPCs regulates the extent of the innate neurogenic repair response in the SVZ after stroke.
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| Overall design |
Using a mouse model of cortical ischemic stroke (photothrombotic ischemia, PT), we performed single-cell RNA sequencing (scRNAseq) on neural stem progenitor cells (NSPCs) and microglia. Tamoxifen-treated Nestin-CreERT2:R26-yfp transgenic mice underwent PT after injection of photosensitive dye and light exposure. Subventricular zone (SVZ) compartments were microdissected from brains of control (Ctrl, no PT), 1 day post-PT (S1d), and 7 days post-PT (S7d) animals. SVZ tissue was digested enzymatically and dissociated mechanically, and GFP+ SVZ NSPCs and CD11b+CD45low microglia were FACS isolated before scRNAseq and library prep using the plate-based mCEL-Seq2 protocol. cDNA libraries were sequenced with Illumina HiSeq 3000. Reads were demultiplexed with bcl2fastq and aligned to the GRCm39 mouse reference genome.
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| Contributor(s) |
Nath S, Carlos Martinez Santamaria J, Chu Y, Choi JS, Conforti P, Lin J, Sankowski R, Amann L, Galanis C, Wu K, Deshpande SS, Vlachos A, Prinz M, Lee JK, Schachtrup C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 29, 2024 |
| Last update date |
Sep 05, 2024 |
| Contact name |
James S Choi |
| E-mail(s) |
jsc228@miami.edu
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| Organization name |
University of Miami Miller School of Medicine
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| Street address |
1095 NW 14th Terrace
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| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1153921 |
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