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| Status |
Public on Aug 21, 2020 |
| Title |
Targeting Piezo1 Unleashes Innate Immunity Against Cancer and Infectious Disease |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor-immunity, is not well-studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We discovered signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells. Moreover, deletion of Piezo1 in myeloid cells protected against cancer and increased survival in poly-microbial sepsis. Mechanistically, we show that mechanical stimulation promotes Piezo1-dependent myeloid cell expansion by suppressing Rb. We further show Piezo1-mediated silencing of Rb is regulated via upregulation of HDAC2. Collectively, our work uncovers Piezo1 as a targetable immune checkpoint that drives immune-suppressive myelopoiesis in cancer and infectious disease.
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| Overall design |
For single cell Seq and ChIP-Seq experiments, mouse Piezo1f/f;LyzMCre and Piezo1f/f bone marrow cells were negatively enriched for CD3-CD19-Ter119- cells using FACS-sorting.
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| Contributor(s) |
Aykut B, Khodadadi-Jamayran A, Miller G |
| Citation(s) |
32826342 |
| |
| Submission date |
Jul 29, 2020 |
| Last update date |
Nov 20, 2020 |
| Contact name |
Alireza Khodadadi-Jamayran |
| Organization name |
New York University, NYU Langone Medical Center
|
| Department |
Division of Advanced Research Technologies (DART)
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| Lab |
Applied Bioinformatics Laboratories (ABL)
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| Street address |
550 1st Ave, MSB 304
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| City |
New York City |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA649429 |
| SRA |
SRP274087 |
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