ZFIN ID: ZDB-PUB-170815-11
The Vascular Niche Regulates Hematopoietic Stem and Progenitor Cell Lodgment and Expansion via klf6a-ccl25b
Xue, Y., Lv, J., Zhang, C., Wang, L., Ma, D., Liu, F.
Date: 2017
Source: Developmental Cell   42(4): 349-362.e4 (Journal)
Registered Authors: Liu, Feng, Ma, Dongyuan, Wang, Lu, Zhang, Chunxia
Keywords: caudal hematopoietic tissue, ccl25b, hematopoietic stem and progenitor cells, klf6a, niche
Microarrays: GEO:GSE98426
MeSH Terms:
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Chemokines, CC/genetics
  • Chemokines, CC/metabolism*
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Receptors, CCR7/metabolism
  • Stem Cell Niche*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28803829 Full text @ Dev. Cell
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.