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

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 differ...

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Published inStem cell reports Vol. 19; no. 1; pp. 112 - 125
Main Authors Nguyen, Linh Thuy, Zimmermann, Karin, Kowenz-Leutz, Elisabeth, Lim, Ramonique, Hofstätter, Maria, Mildner, Alexander, Leutz, Achim
Format Journal Article
LanguageEnglish
Published United States Elsevier 09.01.2024
Subjects
Animals
Biology
Cell Differentiation
Cell Transdifferentiation
Granulocytes - metabolism
Hematopoiesis
Mice
Monocytes
Resource
C/EBP
leukemia
hematopoiesis
cell fate
myelopoiesis
transdifferentiation
GMP
granulocyte-macrophage progenitor
3R principles
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Summary: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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These authors contributed equally
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2023.11.011