Developing HSCs become Notch independent by the end of maturation in the AGM region.

Autor:	Souilhol C; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Lendinez JG; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Rybtsov S; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Murphy F; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Wilson H; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Hills D; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Batsivari A; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Binagui-Casas A; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, McGarvey AC; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, MacDonald HR; Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland;, Kageyama R; Institute for Virus Research, University of Kyoto, Kyoto, Japan; and., Siebel C; Department of Discovery Oncology, Genentech, South San Francisco, CA., Zhao S; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;, Medvinsky A; Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine Bioquarter, University of Edinburgh, Edinburgh, United Kingdom;
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2016 Sep 22; Vol. 128 (12), pp. 1567-77. Date of Electronic Publication: 2016 Jul 15.
DOI:	10.1182/blood-2016-03-708164
Abstrakt:	The first definitive hematopoietic stem cells (dHSCs) in the mouse emerge in the dorsal aorta of the embryonic day (E) 10.5 to 11 aorta-gonad-mesonephros (AGM) region. Notch signaling is essential for early HSC development but is dispensable for the maintenance of adult bone marrow HSCs. How Notch signaling regulates HSC formation in the embryo is poorly understood. We demonstrate here that Notch signaling is active in E10.5 HSC precursors and involves both Notch1 and Notch2 receptors, but is gradually downregulated while they progress toward dHSCs at E11.5. This downregulation is accompanied by gradual functional loss of Notch dependency. Thus, as early as at final steps in the AGM region, HSCs begin acquiring the Notch independency characteristic of adult bone marrow HSCs as part of the maturation program. Our data indicate that fine stage-dependent tuning of Notch signaling may be required for the generation of definitive HSCs from pluripotent cells. (© 2016 by The American Society of Hematology.)
Databáze:	MEDLINE
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