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

ABSTRACT: The CCAAT/enhancer-binding-protein beta (C/EBPβ) 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/EBPβ 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE248415 | GEO | 2023/11/24

REPOSITORIES: GEO

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