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




Nguyen Linh Thuy, Zimmermann Karin, Kowenz-Leutz Elisabeth, Lim Ramonique, Hofstätter Maria, Mildner Alexander, Leutz Achim

PublisherElsevier

2024

Stem Cell Reports

Stem Cell Reports

19

1

112

125

2213-6711

2213-6711

DOIhttps://doi.org/10.1016/j.stemcr.2023.11.011

https://doi.org/10.1016/j.stemcr.2023.11.011

https://research.utu.fi/converis/portal/detail/Publication/386853943



CCAAT/enhancer-binding protein beta (C/EBPβ) induces primary v-Abl immortalized mouse B cells to transdifferentiate (BT, B cell transdifferentiation) into granulocyte-macrophage progenitor-like cells (GMPBTs). GMPBTs maintain cytokine-independent self-renewal, lineage choice, and multilineage differentiation. Single-cell transcriptomics demonstrated that GMPBTs comprise a continuum of myelomonopoietic differentiation states that seamlessly fit into state-to-fate maps of normal granulocyte-macrophage progenitors (GMPs). 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 but 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.


Last updated on 2025-11-02 at 15:24