RT Journal Article
SR Electronic
T1 Hematopoietic progenitors polarize in contact with bone marrow stromal cells by engaging CXCR4 receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.11.089292
DO 10.1101/2020.05.11.089292
A1 Thomas Bessy
A1 Benoit Souquet
A1 Benoit Vianay
A1 Alexandre Schaeffer
A1 Thierry Jaffredo
A1 Jerome Larghero
A1 Laurent Blanchoin
A1 Stephane Brunet
A1 Lionel Faivre
A1 Manuel Théry
YR 2020
UL http://biorxiv.org/content/early/2020/05/13/2020.05.11.089292.abstract
AB Hematopoietic stem and progenitor cells (HSPCs) are located in the bone marrow, where they regulate the permanent production and renewal of all blood-cell types. HSPC proliferation and differentiation is locally regulated by their interaction with cells forming specific microenvironments close to the bone matrix or close to blood vessels. However, the cellular mechanisms underlying HSPC’s interaction with these cells and their potential impact on HSPC polarity is still poorly understood. Here we modelled the bone-marrow niche using microfluidic technologies in a bone-marrow on a chip device, and evaluated long-duration cell-cell contacts between single HSPCs and stromal cells or endothelial cells in a custom-designed microwell cell-culture system. We found that an HSPC can form a discrete contact site that leads to the extensive polarization of their cytoskeleton architectures. As in the case with immune synapses formed by lymphocytes, the centrosome was located in proximity of the cell-cell contact. The entire microtubule network emanated from the centrosome, and the nucleus was confined to the side opposite of the cell-cell contact. The capacity of the HSPC to polarize appeared specific as it was not observed in contact with skin fibroblasts. The receptors ICAM, VCAM and CXCR4 were identified in the polarizing contact, and were all independently capable of inducing morphological polarization. However, only CXCR4 was independently capable of inducing the polarization of the centrosome-microtubule network. Altogether these results revealed a novel mechanism of HSPC polarization associated with its anchorage to specific cells in the bone-marrow, which might be instrumental in the regulation of their fate.Competing Interest StatementThe authors have declared no competing interest.