PU.1 is required to restrain myelopoiesis during chronic inflammatory stress

Chronic inflammation is a common feature of aging and numerous diseases such as diabetes, obesity, autoimmune syndromes has been linked to the development hematological malignancy. Blood-forming hematopoietic stem cells (HSC) can contribute these via production tissue-damaging myeloid and/or acquisition mutations in epigenetic transcriptional regulators that initiate evolution toward leukemogenesis. We previously showed “master regulator” transcription factor PU.1 robustly induced HSC by pro-inflammatory cytokines interleukin (IL)-1β limits their proliferative activity. Here, we used PU.1-deficient mouse model investigate broader role regulating activity response chronic inflammatory challenges. found critical restraining myelopoiesis suppression cell cycle self-renewal gene programs myeloid-biased multipotent progenitor (MPP) cells. Our data show while functions key driver differentiation, it plays an equally tailoring responses stimuli limiting expansion expression MPPs. These identify regulator “emergency” relevant disease