GSE120111
Sca1+ macrophages activate hematopoietic stem/progenitor cells upon bone marrow stress. [RNA-Seq]
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. Overall design: Lin- Sca1+ c-Kit+ (LSK) cells from CAG-EGFP mice were transplanted into steady-state control or 5-FU treated WT mice. Conditioning by 5-FU (200mg/kg) was performed 2 days before transplantation. Twenty-four hours after transplantation, EGFP+ cells in recipient BM were sorted from 2 groups and conducted RNA-seq analyses.