Nucleoporin Nup358 drives the differentiation of myeloid-biased multipotent progenitors by modulating HDAC3 nuclear translocation

We report that Nup358, a nucleoporin linked to acute myeloid leukemia and myeloproliferative neoplasms, is required for the developmental progression of early myeloid progenitors. We found that loss of Nup358 in mice is associated with the accumulation of myeloid-primed multipotent progenitors (MPPs) in bone marrow and the loss of myeloid-committed progenitors and mature myeloid cells. Accumulated MPPs in Nup358 knockout mice are greatly restricted to megakaryocyte/erythrocyte biased MPP2 cells and fail to progress into committed myeloid progenitors. Bone marrow cells were stained for flow cytometry with Lin antibody cocktail and with antibodies against Sca1 and cKit and gene expression analyzed using 10X Genomic scRNA-seq protocol.