Fig. 6: Effects of IL-1β on gene expression in Jak2V617F mice hematopoietic progenitors.

a Volcano plot showing significantly upregulated and downregulated (p-adj < 0.05 and log₂fc > 0.5) genes in in LSK cells isolated from Jak2^VF/+ mice treated with vehicle (PBS) (n = 3) or IL-1β (n = 2). b Gene-set enrichment analysis (GSEA). Gene sets of myeloid cell development, MYC targets, mTORC1 signaling and translation are enriched in LSK cells from Jak2^VF/+ mice treated with IL-1β (n = 2) compared to PBS (n = 3). c Venn diagram showing the overlap between upregulated genes in MF patient granulocytes²¹ (n = 62 for MF, n = 23 for control) and genes upregulated in IL-1β treated Jak2^VF/+ LSK cells (n = 2 for IL-1β treated, n = 3 for PBS treated). The cutoffs were FDR-adjusted p < 0.05. Overlapping genes showed enrichment for MYC targets, mTORC1 signaling, translation and myeloid development gene signatures. d Heat maps of selected upregulated transcripts related to MYC targets, mTORC1 signaling, translation and myeloid development gene signatures in LSK cells from Jak2^VF/+ mice treated with IL-1β (n = 2) compared to PBS (n = 3) (FDR < 0.05). Gene transcripts shown in bold were further validated. e RT-qPCR validation of Lcn2, Clec5a, Odc1, Bcat1 and Eif4a1 mRNA expression in LSK cells from Jak2^VF/+ mice treated with IL-1β compared to PBS. RT-qPCR results were normalized with Hprt1 expression (n = 3 biological replicates per group). f CFU-GM colonies were assessed following overexpression of Lcn2, Clec5a and Bcat1 in Jak2^VF/+ BM. CFU-GM colonies relative to vector control are shown in bar graphs as mean ± SEM (n = 6 biological replicates per group; each data point is an average of two technical replicates). g Megakaryocytic (Mk) cells were derived from the Jak2^VF/+ BM overexpressing vector, Lcn2, Clec5a and Bcat1, and cell proliferation was assessed in triplicates every 2 days over 6 days using Cell Titer Glow. Megakaryocytic cell proliferation relative to vector control are shown in bar graphs as mean ± SEM (n = 5 biological replicates per group; each data point is an average of two technical replicates). Statistical significances were determined in e–g using multiple unpaired two-tailed t-tests. Source data are provided as a Source Data file.