Monocytes generated by interleukin-6-treated human hematopoietic stem and progenitor cells secrete calprotectin that inhibits erythropoiesis.
Elevated circulating levels of calprotectin (CAL), the S100A8/A9 heterodimer, are biomarkers of severe systemic inflammation. Here, we investigate the effects of CAL on early human hematopoiesis. CAL demonstrates limited impact on gene expression in stem and progenitor cells, in contrast with interleukin-6 (IL6), which promotes the expression of the S100A8 and S100A9 genes in hematopoietic progenitors and the generation of monocytes that release CAL. The main target of CAL is an erythroid-megakaryocyte progenitor (EMP) subset. CAL prevents both erythropoietin-driven differentiation of healthy progenitors and JAK2-V617F-driven erythropoiesis. In the context of JAK2-V617F, CAL also promotes the expression of S100A8 and S100A9 genes in monocytes. The signature of CAL effects is detected in the bone marrow progenitors of patients with myeloid malignancy or severe infection. These results position CAL as a mediator of IL6 effects on triggering anemia during inflammation, an effect that is amplified in the context of JAK2-V617F-driven hematopoiesis.
Pubmed ID: 39811665 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
- UniProt (RRID:SCR_002380)
- Gene Set Enrichment Analysis (RRID:SCR_003199)
- ProteomeXchange (RRID:SCR_004055)
- Jackson Laboratory (RRID:SCR_004633)
- HTSeq (RRID:SCR_005514)
- PeproTech (RRID:SCR_006802)
- KEGG (RRID:SCR_012773)
- TopHat (RRID:SCR_013035)
- BD Biosciences (RRID:SCR_013311)
- MaxQuant (RRID:SCR_014485)
- ggplot2 (RRID:SCR_014601)
- Bowtie 2 (RRID:SCR_016368)
- GENCODE (RRID:SCR_014966)
- bcl2fastq (RRID:SCR_015058)
- DESeq2 (RRID:SCR_015687)
- Perseus (RRID:SCR_015753)
- Seurat (RRID:SCR_016341)
- factoextra (RRID:SCR_016692)
- clusterProfiler (RRID:SCR_016884)
- KEGG PATHWAY Database (RRID:SCR_018145)
- Bustools (RRID:SCR_018210)
- Azimuth (RRID:SCR_021084)
- AnnotationDbi (RRID:SCR_023487)
- Bio-Rad QuantaSoft Analysis Pro (RRID:SCR_025321)
Antibodies used in this publication
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This is a list of tools and resources that we have found mentioned in this publication.
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