A1 Refereed original research article in a scientific journal
C/EBPβ-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor biology
Authors: Nguyen Linh Thuy, Zimmermann Karin, Kowenz-Leutz Elisabeth, Lim Ramonique, Hofstätter Maria, Mildner Alexander, Leutz Achim
Publisher: Elsevier
Publication year: 2024
Journal: Stem Cell Reports
Journal name in source: Stem Cell Reports
Volume: 19
Issue: 1
First page : 112
Last page: 125
ISSN: 2213-6711
eISSN: 2213-6711
DOI: https://doi.org/10.1016/j.stemcr.2023.11.011
Web address : https://doi.org/10.1016/j.stemcr.2023.11.011
Self-archived copy’s web address: 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.
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