Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways Journal Article
| Authors: | Westerterp, M.; Gourion-Arsiquaud, S.; Murphy, A. J.; Shih, A.; Cremers, S.; Levine, R. L.; Tall, A. R.; Yvan-Charvet, L. |
| Article Title: | Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways |
| Abstract: | Intact cholesterol homeostasis helps to maintain hematopoietic stem and multipotential progenitor cell (HSPC) quiescence. Mice with defects in cholesterol efflux pathways due to deficiencies of the ATP binding cassette transporters ABCA1 and ABCG1 displayed a dramatic increase in HSPC mobilization and extramedullary hematopoiesis. Increased extramedullary hematopoiesis was associated with elevated serum levels of G-CSF due to generation of IL-23 by splenic macrophages and dendritic cells. This favored hematopoietic lineage decisions toward granulocytes rather than macrophages in the bone marrow leading to impaired support for osteoblasts and decreased Cxcl12/SDF-1 production by mesenchymal progenitors. Greater HSPC mobilization and extramedullary hematopoiesis were reversed by raising HDL levels in Abca1 -/-Abcg1 -/- and Apoe -/- mice or in a mouse model of myeloproliferative neoplasm mediated by Flt3-ITD mutation. Our data identify a role of cholesterol efflux pathways in the control of HSPC mobilization. This may translate into therapeutic strategies for atherosclerosis and hematologic malignancies. © 2012 Elsevier Inc. |
| Keywords: | controlled study; myeloproliferative disorders; nonhuman; protein blood level; animal cell; mouse; animals; mice; mice, knockout; atp-binding cassette transporters; dendritic cell; vascular cell adhesion molecule 1; mice, inbred c57bl; cell lineage; mice, transgenic; hematologic malignancy; regulatory mechanism; messenger rna; atherosclerosis; nerve cell adhesion molecule; stem cell mobilization; hematopoietic stem cells; cell movement; stem cells; mesenchymal stem cell; hematopoiesis; cholesterol; hematopoietic stem cell; interleukin 17; mouse strain; disease models, animal; macrophage; homeostasis; cxcl2 chemokine; nestin; granulocyte colony stimulating factor; biological transport; cd45 antigen; granulocyte; myeloproliferative neoplasm; osteoblast; cd51 antigen; cd31 antigen; stromal cell derived factor 1; vascular endothelial cadherin; macrophage inflammatory protein 2; interleukin 23; extramedullary hematopoiesis; dipeptidyl peptidase iv; high density lipoprotein; lipoproteins; interleukin 3; ataxin 1; mice, inbred dba; osteocalcin; apolipoprotein a-i; abc transporter a1; abc transporter g1; cholesterol transport; splenic macrophage |
| Journal Title: | Cell Stem Cell |
| Volume: | 11 |
| Issue: | 2 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2012-08-03 |
| Start Page: | 195 |
| End Page: | 206 |
| Language: | English |
| DOI: | 10.1016/j.stem.2012.04.024 |
| PROVIDER: | scopus |
| PMCID: | PMC3413200 |
| PUBMED: | 22862945 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 4 September 2012" - "Source: Scopus" |
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