The Vascular Niche Regulates Hematopoietic Stem and Progenitor Cell Lodgment and Expansion via klf6a-ccl25b

Publication date: Available online 10 August 2017
Source:Developmental Cell
Author(s): Yuanyuan Xue, Junhua Lv, Chunxia Zhang, Lu Wang, Dongyuan Ma, Feng Liu
In mammals, hematopoietic stem and progenitor cells (HSPCs) rapidly expand in the fetal liver (FL), but the underlying mechanism remains unclear. Here, we characterize zebrafish caudal hematopoietic tissue (CHT) and identify an important cellular and molecular mechanism of HSPC expansion. Time-lapse imaging showed that HSPCs localize adjacent to vascular endothelial cells (ECs), and their migration and expansion display caudal vein-specific orientation in the CHT. RNA sequencing and functional analysis identified that an EC-expressed transcription factor, Krüppel-like factor 6a (Klf6a), is essential for the CHT niche. We further demonstrated that Klf6a directly regulates the expression of the chemokine (C-C motif) ligand 25b to modulate HSPC lodgment and proliferation. Ex vivo culture results support the conserved role of Ccl21/Ccr7 signaling in promoting HSPC expansion in mammals. Together, we identify the Klf6a-Ccl25b/Ccr7 axis in controlling the complex HSPC-CHT niche interaction, which may be applicable to in vitro expansion or engraftment of HSPCs after transplantation.

Graphical abstract

Teaser

The molecular mechanisms underlying hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Xue et al. reveal that vascular niche-derived chemokine signals are required for HSPC lodgment and expansion in the zebrafish caudal hematopoietic tissue.


http://ift.tt/2vUCop1