C/EBPß-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor (GMP) biology

The CCAAT/enhancer-binding-protein beta (C/EBPß) induces primary v-Abl immortalized mouse B cell transdifferentiation (BT) into granulocyte-macrophage-progenitor-like cells (GMPBT). GMPBT maintain cytokine independent self-renewal, lineage choice, and multi-lineage differentiation. Single cell transcriptomics now shows that GMPBT comprise a continuum of myelomonopoietic differentiation states that seamlessly fit into state-to-fate maps of normal GMP. Inactivation of the v-Abl kinase unveiled dependence on activated CSF2-Jak2-Stat5 signaling. Deletion of IRF8 diminished monopoiesis and enhanced granulopoiesis while removal of C/EBPß abrogated self-renewal and granulopoiesis yet permitted macrophage differentiation. The GMPBT cell culture system is easily scalable to explore the basics of GMP biology and lineage commitment and largely reduces ethically and legislatively arguable, labor-intensive, and costly animal experiments. Overall design: v-Abl-transformed mouse pre-B cells were retrovirally infected with rat Cebpb LAP* to induce transdifferentiation. Infected cells were isolated by Fluoresence-activated cell sorting based on EGFP signal on day 6 post-infection and subjected to scRNA-seq analysis.