NACA deficiency reveals the crucial role of somite-derived stromal cells in haematopoietic niche formation

Emi Murayama (), Milka Sarris, Michael Redd, Dorothée Le Guyader, Catherine Vivier, Wyatt Horsley, Nikolaus Trede and Philippe Herbomel ()
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Emi Murayama: Institut Pasteur
Milka Sarris: Institut Pasteur
Michael Redd: University of Utah, Huntsman Cancer Institute
Dorothée Le Guyader: Institut Pasteur
Catherine Vivier: Institut Pasteur
Wyatt Horsley: University of Utah, Huntsman Cancer Institute
Nikolaus Trede: University of Utah, Huntsman Cancer Institute
Philippe Herbomel: Institut Pasteur

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract The ontogeny of haematopoietic niches in vertebrates is essentially unknown. Here we show that the stromal cells of the caudal haematopoietic tissue (CHT), the first niche where definitive haematopoietic stem/progenitor cells (HSPCs) home in zebrafish development, derive from the caudal somites through an epithelial–mesenchymal transition (EMT). The resulting stromal cell progenitors accompany the formation of the caudal vein sinusoids, the other main component of the CHT niche, and mature into reticular cells lining and interconnecting sinusoids. We characterize a zebrafish mutant defective in definitive haematopoiesis due to a deficiency in the nascent polypeptide-associated complex alpha subunit (NACA). We demonstrate that the defect resides not in HSPCs but in the CHT niche. NACA-deficient stromal cell progenitors initially develop normally together with the sinusoids, and HSPCs home to the resulting niche, but stromal cell maturation is compromised, leading to a niche that is unable to support HSPC maintenance, expansion and differentiation.

Date: 2015
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DOI: 10.1038/ncomms9375

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