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| Status |
Public on Nov 25, 2019 |
| Title |
UM171 induces a homeostatic inflammatory-detoxification response supporting human HSC self-renewal |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Elucidation of the molecular cues required to balance adult stem cell self-renewal and differentiation is critical for advancing cellular therapies. Herein, we report that the hematopoietic stem cell (HSC) self-renewal agonist UM171 triggers a balanced pro- and anti-inflammatory/detoxification network that relies on NFKB activation and protein C receptor-dependent ROS detoxification, respectively. We demonstrate that within this network, EPCR serves as a critical protective component as its deletion hypersensitizes primitive hematopoietic cells to pro-inflammatory signals and ROS accumulation resulting in compromised stem cell function. Conversely, abrogation of the pro-inflammatory activity of UM171 through treatment with dexamethasone, cAMP elevating agents or NFKB inhibitors abolishes EPCR upregulation and HSC expansion. Together, these results show that UM171 stimulates ex vivo HSC expansion by establishing a critical balance between key pro- and anti-inflammatory mediators of self-renewal.
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| Overall design |
Human HSC self-renewal
Single cell sequencing of CD34+ cord blood cells exposed to UM171 for 2 days
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| Contributor(s) |
Sauvageau G, Chagraoui J, Lehnertz B |
| Citation(s) |
31703090 |
| Submission date |
Oct 10, 2019 |
| Last update date |
Nov 25, 2019 |
| Contact name |
Guy Sauvageau |
| Organization name |
Institute for Research in Immunology and Cancer
|
| Street address |
2950, Chemin de Polytechnique
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| City |
Montreal |
| State/province |
QC |
| ZIP/Postal code |
H3T 1J4 |
| Country |
Canada |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA576785 |
| SRA |
SRP225033 |
