C/EBPβ-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor biology
Autor/innen
- L.T. Nguyen
- K. Zimmermann
- E. Kowenz-Leutz
- R. Lim
- M. Hofstätter
- A. Mildner
- A. Leutz
Journal
- Stem Cell Reports
Quellenangabe
- Stem Cell Rep 19 (1): 112-125
Zusammenfassung
CCAAT/enhancer-binding protein beta (C/EBPβ) induces primary v-Abl immortalized mouse B cells to transdifferentiate (BT) into granulocyte-macrophage progenitor-like cells (GMPBT). GMPBT maintain cytokine-independent self-renewal, lineage choice, and multilineage differentiation. Single-cell transcriptomics demonstrated that GMPBT comprise a continuum of myelomonopoietic differentiation states that seamlessly fit into state-to-fate maps of normal GMP. Inactivating v-Abl kinase revealed the dependence on activated CSF2-JAK2-STAT5 signaling. Deleting IRF8 diminished monopoiesis and enhanced granulopoiesis while removing C/EBPβ abrogated self-renewal and granulopoiesis yet permitted macrophage differentiation. The GMPBT culture system is easily scalable to explore the basics of GMP biology and lineage commitment and largely reduces ethically and legislatively debatable, labor-intensive, and costly animal experiments.