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Role of N‐cadherin in the regulation of hematopoietic stem cells in the bone marrow niche
Author(s) -
Arai Fumio,
Hosokawa Kentaro,
Toyama Hirofumi,
Matsumoto Yoshiko,
Suda Toshio
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06576.x
Subject(s) - haematopoiesis , stem cell , cadherin , microbiology and biotechnology , progenitor cell , bone marrow , biology , hematopoietic stem cell , cell adhesion molecule , cell adhesion , extracellular matrix , transplantation , cell , immunology , medicine , genetics
Cell–cell and cell–extracellular matrix interactions between hematopoietic stem cells (HSCs) and their niches are critical for the maintenance of stem cell properties. Here, it is demonstrated that a cell adhesion molecule, N‐cadherin, is expressed in hematopoietic stem/progenitor cells (HSPCs) and plays a critical role in the regulation of HSPC engraftment. Furthermore, overexpression of N‐cadherin in HSCs promoted quiescence and preserved HSC activity during serial bone marrow (BM) transplantation (BMT). Inhibition of N‐cadherin by the transduction of N‐cadherin short hairpin (sh) RNA (shN‐cad) reduced the lodgment of donor HSCs to the endosteal surface, resulting in a significant reduction in long‐term engraftment. shN‐cad‐transduced cells were maintained in the spleen for six months after BMT, indicating that N‐cadherin expression in HSCs is specifically required in the BM. These findings suggest that N‐cadherin‐mediated cell adhesion is functionally essential for the regulation of HSPC activities in the BM niche.