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| Status |
Public on Aug 31, 2022 |
| Title |
Parenchymal border macrophages regulate CSF flow dynamics [5xFAD] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Microglial cells are the resident macrophages of the brain. Perivascular macrophages (PVM) are also myeloid resident cells that are located at the interface between blood, CSF and brain in the perivascular space. Due to their strategic location and their ability to sample CSF content, we hypothesized that PVM might play a role in CSF flow. Using different fluorescent tracers injected either into the CSF (influx) or the brain parenchyma (efflux) we assessed their spatio-temporal distribution and found that ablation (using clodronate liposomes) or dysfunction (using genetic tools) of PVM alters CSF dynamics and patterns. Using single cell RNA sequencing, we found that PBMs can be divided in two sub-populations, and that one population of PBMs could interact with vascular smooth muscle cells, which allow arterial pulsations and subsequently CSF flow. Interestingly, aging results in altered PVM phenotype, and reversing this phenotype using macrophage specific grown factors reversed some of aging-associated dysfunctions of CSF flow. In summary, our results identify a new role of PVM in CSF flow and open new avenues for therapeutical applications targeting PVM in neurodegenerative diseases such as Alzheimer’s disease.
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| Overall design |
Mice received a lethal intraperitoneal injection of euthasol (10% v/v in saline, 250ml), and transcardially perfused with PBS containing 10U/ml heparin. Cortex were gently dissected in PBS, digested and stained after myelin removal with CD13 (to stain for mural cells), CD31 (endothelial cells), and CD45 (immune cells). Stromal cells (i.e., endothelial+mural) and immune cells were then sorted and prepared for single cell sequencing.
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| Contributor(s) |
Drieu A, Dykstra T, Kipnis J |
| Citation(s) |
36352225 |
| |
| Submission date |
Jun 14, 2022 |
| Last update date |
Nov 18, 2022 |
| Contact name |
Jonathan Kipnis |
| Organization name |
Washington University in Saint Louis
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| Department |
Pathology and Immunology
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| Lab |
Kipnis Lab
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| Street address |
4515 McKinley Ave
|
| City |
Saint Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE188285 |
Parenchymal border macrophages regulate CSF flow dynamics |
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| Relations |
| BioProject |
PRJNA849229 |
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