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Series GSE138680 Query DataSets for GSE138680
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
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.
Overall design Human HSC self-renewal
Single cell sequencing of CD34+ cord blood cells exposed to UM171 for 2 days
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
City Montreal
State/province QC
ZIP/Postal code H3T 1J4
Country Canada
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (3)
GSM4116047 CD34+ cord blood cells, d2_DMSO
GSM4116048 CD34+ cord blood cells, d2_UM171_35nM
GSM4116049 CD34+ cord blood cells, d2_UM171_1000nM
BioProject PRJNA576785
SRA SRP225033

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Supplementary file Size Download File type/resource
GSE138680_exprMatrix.tsv.gz 466.1 Mb (ftp)(http) TSV
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