Fig. 2: IL1β drives expansion, myeloid bias, and enhances self-renewal of Tet2-KO HSPCs. | Nature Communications

Fig. 2: IL1β drives expansion, myeloid bias, and enhances self-renewal of Tet2-KO HSPCs.

From: Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells

Fig. 2: IL1β drives expansion, myeloid bias, and enhances self-renewal of Tet2-KO HSPCs.The alternative text for this image may have been generated using AI.

a, b Lineage-depleted BM cells from wild-type (WT) CD45.1+ and Rosa-rtTA-driven inducible Tet2 knockdown (shTet2) CD45.2 mice transplanted into lethally irradiated WT CD45.1+CD45.2+ mice and treated with IL1β or vehicle as well as with and without doxycycline (withdrawal; dox w/d) as described in Fig. 1d and analyzed by flow cytometry (n = 5 for Veh, IL1β, Dox w/d IL1β, 4 for Dox w/d mice/group). a Percentage of live cells which are LT-HSCs and b MPP2, MPP3, and MPP4 in the BM and spleen of shTet2 and WT mice. c The ratio of the change in frequency between dox to dox w/d for MPP2s, MPP3s, and MPP4s in BM. d Colony-forming unit (CFU) assay of sorted LSK cells from WT or Tet2-KO BM (n = 9 technical replicates with 3 biological replicates); colonies were counted and the cells were re-plated every 7 days. M, macrophage; G, granulocyte; GM, granulocyte/macrophage; BFU-E, erythroid. e Simplified hematopoietic hierarchy with red text representing subsets elevated in frequency in Tet2-KO relative to WT mice treated with IL1β with red arrows connecting the most elevated subsets. Error bars represent mean ± SEM. For panels, a, b, and d, two-factor ANOVA was used to determine FWER-adjusted p values. For panel c, one factor ANOVA was used to determine the FWER-adjusted p values. For all FWER adjusted p values: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

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