A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

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




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

KustantajaElsevier

Julkaisuvuosi2024

JournalStem Cell Reports

Tietokannassa oleva lehden nimiStem Cell Reports

Vuosikerta19

Numero1

Aloitussivu112

Lopetussivu125

ISSN2213-6711

eISSN2213-6711

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

Verkko-osoitehttps://doi.org/10.1016/j.stemcr.2023.11.011

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/386853943


Tiivistelmä

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