| First Author | Hosokawa K | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 4 | Pages | 554-63 |
| PubMed ID | 20427705 | Mgi Jnum | J:162799 |
| Mgi Id | MGI:4819906 | Doi | 10.1182/blood-2009-05-224857 |
| Citation | Hosokawa K, et al. (2010) Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. Blood 116(4):554-63 |
| abstractText | During postnatal life, the bone marrow (BM) supports both self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized microenvironments termed stem cell niches. Cell-cell and cell-extracellular matrix interactions between HSCs and their niches are critical for the maintenance of HSC properties. Here, we analyzed the function of N-cadherin in the regulation of the proliferation and long-term repopulation activity of hematopoietic stem/progenitor cells (HSPCs) by the transduction of N-cadherin shRNA. Inhibition of N-cadherin expression accelerated cell division in vitro and reduced the lodgment of donor HSPCs to the endosteal surface, resulting in a significant reduction in long-term engraftment. Cotransduction of N-cadherin shRNA and a mutant N-cadherin that introduced the silent mutations to shRNA target sequences rescued the accelerated cell division and reconstitution phenotypes. In addition, the requirement of N-cadherin for HSPC engraftment appears to be niche specific, as shN-cad-transduced lineage(-)Sca-1(+)c-Kit(+) cells successfully engrafted in spleen, which lacks an osteoblastic niche. These findings suggest that N-cad-mediated cell adhesion is functionally required for the establishment of hematopoiesis in the BM niche after BM transplantation. |
