Interleukin-1β modulates lymphoid differentiation of Flt3-positive multipotent progenitors after transplantation

Myeloablative pre-conditioning facilitates the differentiation of transplanted hematopoietic stem and progenitor cells (HSPCs). However, the factors in the stress environment that regulate HSPC behavior remain elusive. Here, we investigated the mechanisms that shaped the cell fates of transplanted murine multipotent progenitors (MPPs) expressing the Fms-related receptor tyrosine kinase 3 gene (Flt3). Using lineage tracing, clonal analysis, and single-cell RNA sequencing (RNA-seq), we showed that the myeloablative environment increased lymphoid priming of Flt3⁺ MPPs and that their efficient B cell output required intact interleukin 1 (IL-1) signaling. The Flt3⁺ MPPs with short-term exposure to IL-1β underwent a myeloid-biased to lymphoid-biased cell fate switch and produced more lymphoid-biased progeny with a stronger B lymphopoiesis capacity in vitro. Correspondingly, a brief exposure to IL-1β facilitated the B cell output of transplanted Flt3⁺ MPPs in vivo. Together, our study demonstrated an unrecognized function of IL-1β in promoting B lymphopoiesis and highlighted a latent effect of IL-1β in regulating MPP cell fate dynamics.