N-cadherin is expressed on human hematopoietic progenitor cells and mediates interaction with human mesenchymal stromal cells.
Specific cell-cell junctions between hematopoietic stem cells (HSC) and their niche have been shown to regulate stem cell function. N-cadherin was suggested to play a central role in this process, whereas other studies indicated that it did not play an essential role in the murine model. We have analyzed the role of N-cadherin for interaction between hematopoietic progenitor cells (HPC) and supportive mesenchymal stromal cells (MSC) in a human-human setting. Expression of N-cadherin and of cadherin-11 (osteoblast cadherin) was analyzed in HPC by quantitative RT-PCR, Western blot, and flow cytometry. N-cadherin and cadherin-11 were expressed in HPC at a moderate level, whereas they were not detectable in differentiated cells. Confocal laser scanning microscopy revealed that N-cadherin and beta-catenin are colocalized at the junction of HPC and MSC. siRNA knockdown of N-cadherin or cadherin-11 as well as treatment with the blocking function antibody decreased adhesive interaction of HPC to MSC. Furthermore, knockdown of N-cadherin or blocking function antibody impaired maintenance of long-term culture-initiating cells (LTC-IC) on coculture of HPC and MSC. These results indicate that N-cadherin is involved in the bidirectional interaction of human HPC with their cellular determinants in the niche.
Wein
Frederik
F
Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
Pietsch
Larissa
L
Saffrich
Rainer
R
Wuchter
Patrick
P
Walenda
Thomas
T
Bork
Simone
S
Horn
Patrick
P
Diehlmann
Anke
A
Eckstein
Volker
V
Ho
Anthony D
AD
Wagner
Wolfgang
W
D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015820:Cadherins; C086960:osteoblast cadherin