Data from: Tungsten blocks murine B lymphocyte differentiation and proliferation through downregulation of IL-7 receptor/Pax5 signaling
Wu, Ting Hua et al. (2019), Data from: Tungsten blocks murine B lymphocyte differentiation and proliferation through downregulation of IL-7 receptor/Pax5 signaling, Dryad, Dataset, https://doi.org/10.5061/dryad.63p3r08
Tungsten is an emerging environmental toxicant associated with several pediatric leukemia clusters, although a causal association has not been established. Our previous work demonstrated that tungsten exposure resulted in an accumulation of pre-B cells in the bone marrow, the same cell type that accumulates in pediatric acute lymphoblastic leukemia (ALL). To better understand the relevant molecular mechanisms, we performed RNA sequencing on flow sorted pre-B cells from control and tungsten-exposed mice. Tungsten decreased the expression of multiple genes critical for B cell development, including members of the IL-7R and pre-BCR signaling pathways, such as Jak1, Stat5a, Erb1, Pax5, Syk, and Ikzf3. These results were confirmed in an in vitro model of B cell differentiation, where tungsten arrested differentiation at the pro-B cell stage and inhibited proliferation. These changes were associated with decreased expression of multiple genes in the IL-7R signaling pathway and decreased percentage of IL-7R, phosphorylated STAT5 (pSTAT5) double-positive cells. Supplementation with IL-7 or overexpression of Pax5, the transcription factor downstream of IL-7R, rescued the tungsten-induced differentiation block. Together, these data support the hypothesis that IL-7R/Pax5 signaling axis is critical to tungsten-mediated effects on pre-B cell development. Importantly, many of these molecules are modulated in ALL.