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Meteorin in macrophages regulates hematopoietic stem/progenitor cells

ABSTRACT: Meteorin in macrophages regulates hematopoietic stem/progenitor cells

PROVIDER: PRJNA817079 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18355692_1.fastq.gz	Fastqsanger.gz
	SRR18355692_2.fastq.gz	Fastqsanger.gz
	SRR18355693_1.fastq.gz	Fastqsanger.gz
	SRR18355693_2.fastq.gz	Fastqsanger.gz
	SRR18355694_1.fastq.gz	Fastqsanger.gz

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Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality

Project description:There are no described quality assurance mechanisms for newly formed stem cells. We observed intimate interactions between macrophages and blood stem cells in zebrafish embryos. Stressed stem cells were marked by surface Calreticulin, which stimulates macrophage interaction as an eat me signal. Macrophage-stem cell interactions either lead to removal of cytoplasmic material and stem cell proliferation or resulted in complete stem cell engulfment. Calreticulin knock down or embryonic macrophage depletion reduced the number of stem cell clones into adulthood. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.

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Meteorin in macrophages regulates hematopoietic stem/progenitor cells

Project description:We show that meteorin (Metrn) from hypoxic macrophages restrains hematopoietic stem cells (HSCs) proliferation and mobilization. In macrophages specific Metrn knockout mice, reactive oxygen species levels in HSCs were upregulated through activating phospholipase C signaling. Macrophage specific knockout mice for Metrn (Metrn-fl/fl*LysM-Cre) were generated. Transcriptome profiling (RNA-Seq) and differential gene expression analysis of bone marrow LSK (lin- sca-1+ c-kit+) cells from Metrn-fl/fl*LysM-Cre (Metrn-cKO) and Metrn-fl/fl mice was performed. Metrn cKO mice showed a regulatory role for HSPCs by macrophages.

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Project description:Sca1+ macrophages activate hematopoietic stem/progenitor cells upon bone marrow stress.

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Sca1+ macrophages activate hematopoietic stem/progenitor cells upon bone marrow stress. [RNA-Seq]

Project description:Sca1+ macrophages activate hematopoietic stem/progenitor cells upon bone marrow stress. [RNA-Seq]

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Project description:Sca1+ macrophages activate hematopoietic stem/progenitor cells upon bone marrow stress. [scRNA-Seq]

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Sca1+ macrophages activate hematopoietic stem/progenitor cells upon bone marrow stress. [scRNA-Seq]

Project description:Although hematopoietic stem and progenitor cells (HSPCs) become activated in the cell-cycle status after chemotherapy to supply hematopoietic loss, the detailed mechanisms of activation remain unknown. Here we show that Sca1+ macrophages play a key role for bone marrow (BM) recovery through granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion. By analyzing gene expression profiles of HSPCs lodged in 5-fluolouracil (5-FU)-treated mice, we found GM-CSF as a key proliferative signal. Sca1+ macrophages in BM after 5-FU treatment expressed high levels of GM-CSF. GM-CSF-knockout mice treated with 5-FU were lethal because of severe BM suppression. Up-regulation of Csf2 in Sca1+ macrophages by 5-FU was suppressed in MyD88-knockout mice, suggesting that TLR signaling via damage-associated molecular patterns caused by cell death is critical for up-regulation of Csf2. In 5-FU treated BM, majority of Sca1+ macrophages and transplanted HSPCs locate perivascular areas. These findings together indicate that Sca1+ macrophages induce HSPCs to proliferate through GM-CSF signaling in the stressed BM environments.

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