Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche
Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche
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DOI：
10.1111/j.1749-6632.2012.06576.x
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Suda, Toshio
中科院分区：
文献类型：
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作者：
Arai, Fumio;Hosokawa, Kentaro;Suda, Toshio
造血干细胞（hsc）及其生态位之间的细胞-细胞和细胞-细胞外基质相互作用对于维持干细胞特性至关重要。本研究表明，细胞粘附分子n -钙粘蛋白在造血干细胞/祖细胞（HSPC）中表达，并在HSPC移植调控中发挥关键作用。此外，在连续骨髓移植（BMT）过程中，造血干细胞中N-cadherin的过表达促进了造血干细胞的静止并保持了造血干细胞的活性。通过n -钙粘蛋白短发夹（sh） RNA（shN-cad）的转导抑制n -钙粘蛋白，减少供体造血干细胞在内皮表面的沉积，导致长期移植的显著减少。BMT后shn -cadherin转导的细胞在脾脏中维持了6个月，表明BMT特异性需要造血干细胞中N-cadherin的表达。这些发现表明，n-钙粘蛋白介导的细胞粘附对于调节HSPC在BM生态位中的活性在功能上是必不可少的。
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.