Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells

Céline Souilhol, Christèle Gonneau, Javier G. Lendinez, Antoniana Batsivari, Stanislav Rybtsov, Heather Wilson, Lucia Morgado-Palacin, David Hills, Samir Taoudi, Jennifer Antonchuk, Suling Zhao and Alexander Medvinsky ()
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Céline Souilhol: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Christèle Gonneau: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Javier G. Lendinez: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Antoniana Batsivari: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Stanislav Rybtsov: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Heather Wilson: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Lucia Morgado-Palacin: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
David Hills: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Samir Taoudi: The Walter and Eliza Hall Institute of Medical Research
Jennifer Antonchuk: STEMCELL Technologies Inc., Vancouver
Suling Zhao: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter
Alexander Medvinsky: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.

Date: 2016
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DOI: 10.1038/ncomms10784

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