Let-7 microRNA-dependent control of leukotriene signaling regulates the transition of hematopoietic niche in mice
| Autor: | Ann C. Zovein, John S. Hawkins, Prajakta Ghatpande, Carlos Lizama, Frank L. Bos, Jerry Lee, Yongbo Peng, Giorgio Lagna, Joan P. Zape, Akiko Hata, Xuan Jiang, Justin Louie |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Ribonuclease III Leukotriene B4 General Physics and Astronomy 129 Strain Inbred C57BL Regenerative Medicine Transgenic Strain Dorsal aorta chemistry.chemical_compound Mice 0302 clinical medicine Stem Cell Research - Nonembryonic - Human Stem Cell Niche Aorta Mice Knockout Leukotriene Microscopy Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Hematology Cell biology Endothelial stem cell Haematopoiesis Liver cardiovascular system Stem Cell Research - Nonembryonic - Non-Human Biotechnology Signal Transduction Mice 129 Strain Knockout Science Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Fluorescence Article 03 medical and health sciences Vascular microRNA Genetics Animals Endothelium Progenitor cell Drosha General Chemistry Stem Cell Research Hematopoietic Stem Cells Hematopoiesis Mice Inbred C57BL MicroRNAs 030104 developmental biology chemistry Microscopy Fluorescence Immunology Endothelium Vascular 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017) Nature Communications Nature communications, vol 8, iss 1 Jiang, X; Hawkins, JS; Lee, J; Lizama, CO; Bos, FL; Zape, JP; et al.(2017). Let-7 microRNA-dependent control of leukotriene signaling regulates the transition of hematopoietic niche in mice. NATURE COMMUNICATIONS, 8. doi: 10.1038/s41467-017-00137-y. UCSF: Retrieved from: http://www.escholarship.org/uc/item/22b5c9x9 |
| ISSN: | 2041-1723 |
| Popis: | Hematopoietic stem and progenitor cells arise from the vascular endothelium of the dorsal aorta and subsequently switch niche to the fetal liver through unknown mechanisms. Here we report that vascular endothelium-specific deletion of mouse Drosha (Drosha cKO), an enzyme essential for microRNA biogenesis, leads to anemia and death. A similar number of hematopoietic stem and progenitor cells emerge from Drosha-deficient and control vascular endothelium, but Drosha cKO-derived hematopoietic stem and progenitor cells accumulate in the dorsal aorta and fail to colonize the fetal liver. Depletion of the let-7 family of microRNAs is a primary cause of this defect, as it leads to activation of leukotriene B4 signaling and induction of the α4β1 integrin cell adhesion complex in hematopoietic stem and progenitor cells. Inhibition of leukotriene B4 or integrin rescues maturation and migration of Drosha cKO hematopoietic stem and progenitor cells to the fetal liver, while it hampers hematopoiesis in wild-type animals. Our study uncovers a previously undefined role of innate leukotriene B4 signaling as a gatekeeper of the hematopoietic niche transition. Hematopoietic stem and progenitor cells are generated first from the vascular endothelium of the dorsal aorta and then the fetal liver but what regulates this switch is unknown. Here, the authors show that changing miRNA biogenesis and leukotriene B4 signaling in mice modulates this switch in the niche. |
| Databáze: | OpenAIRE |
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