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

ABSTRACT: C/EBPβ-induced lymphoid-to-myeloid transdifferentiation emulates granulocyte-monocyte progenitor (GMP) biology

PROVIDER: PRJNA1043711 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26907590.fastq.gz	Fastqsanger.gz
	SRR26907591.fastq.gz	Fastqsanger.gz
	SRR26907592.fastq.gz	Fastqsanger.gz
	SRR26907593.fastq.gz	Fastqsanger.gz
	SRR26907594.fastq.gz	Fastqsanger.gz

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

Project description:The CCAAT/enhancer-binding-protein beta (C/EBPβ) induces primary v-Abl immortalized mouse B cell transdifferentiation (BT) into granulocyte-macrophage-progenitor-like cells (GMPBT). GMPBT maintain cytokine independent self-renewal, lineage choice, and multi-lineage differentiation. Single cell transcriptomics now shows that GMPBT comprise a continuum of myelomonopoietic differentiation states that seamlessly fit into state-to-fate maps of normal GMP. Inactivation of the v-Abl kinase unveiled dependence on activated CSF2-Jak2-Stat5 signaling. Deletion of IRF8 diminished monopoiesis and enhanced granulopoiesis while removal of C/EBPβ abrogated self-renewal and granulopoiesis yet permitted macrophage differentiation. The GMPBT cell culture system is easily scalable to explore the basics of GMP biology and lineage commitment and largely reduces ethically and legislatively arguable, labor-intensive, and costly animal experiments.

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Project description: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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