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| Item Type: | Article |
|---|---|
| Title: | C/EBPβ-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor biology |
| Creators Name: | Nguyen, L.T., Zimmermann, K., Kowenz-Leutz, E., Lim, R., Hofstätter, M., Mildner, A. and Leutz, A. |
| Abstract: | 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. |
| Keywords: | C/EBP, Transdifferentiation, Hematopoiesis, Myelopoiesis, Leukemia, GMP, Granulocyte-Macrophage Progenitor, Cell Fate, 3R Principles, Animals, Mice |
| Source: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 19 |
| Number: | 1 |
| Page Range: | 112-125 |
| Date: | 28 December 2023 |
| Official Publication: | https://doi.org/10.1016/j.stemcr.2023.11.011 |
| PubMed: | View item in PubMed |
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