C/EBPß-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor biology.
Stem Cell Reports
; 19(1): 112-125, 2024 01 09.
Article
in En
| MEDLINE
| ID: mdl-38157851
ABSTRACT
CCAAT/enhancer-binding protein beta (C/EBPß) 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/EBPß-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Granulocytes
Limits:
Animals
Language:
En
Journal:
Stem Cell Reports
Year:
2024
Document type:
Article