GSE127939
Signal-Transducing Adaptor Protein-2 Governs Recovery of B Lineage Lymphocytes during hematopoietic stress.
Signal-transducing adaptor protein-2 (STAP-2) was discovered as a c-fms/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and I?B kinase (IKK) in macrophages, mast cells and T cells. There is additional information about roles in several types of malignant diseases including chronic myeloid leukemia, but none concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this issue and learned that it is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of this lineage and myeloid rebound was unremarkable. Furthermore, all hematological parameters were normal once recovery from transplantation was complete. Overexpression of STAP-2 specifically in lymphoid cells resulted in reduced numbers of late-stage B progenitors within bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. LPS normally suppresses B precursor expansion in response to interleukin 7, but STAP-2 deficiency made them more resistant. Preliminary RNA-Seq analyses indicate many signaling pathways in B progenitors are STAP-2 dependent. These findings suggest STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could suggest ways to speed recovery of humoral immunity following chemotherapy or transplantation. Overall design: To determine the molecular basis for the inefficient B lymphopoiesis in STAP-2 Tg BM, transcriptome analyses were used to identify the pathways regulated by STAP-2 under hematological stress. We evaluated the global gene expression profile of pre-B cells derived from WT and Tg BM under steady-state as well as WT and KO BM 1 month after transplantation by RNA-seq experiments.