Active RHOA favors retention of human hematopoietic stem/progenitor cells in their niche

Journal of Biomedical Science

Dominique Bonnet²  Atul Kumar¹  Fernando Anjos-Afonso²  Bithiah Grace Jaganathan¹ 

[1] Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam, India;Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK

关键词: BM niche;    Stem cell migration;    Hematopoietic stem cells;    RHOA;   

Others  :  823308
DOI  :  10.1186/1423-0127-20-66

 received in 2013-08-17, accepted in 2013-09-10,  发布年份 2013

【 摘 要 】

Background

Hematopoietic stem/progenitor cells (HSPCs) maintain the hematopoietic system by balancing their self-renewal and differentiation events. Hematopoietic stem cells also migrate to various sites and interact with their specific microenvironment to maintain the integrity of the system. Rho GTPases have been found to control the migration of hematopoietic cells and other cell types. Although the role of RAC1, RAC2 and CDC42 has been studied, the role of RHOA in human hematopoietic stem cells is unclear.

Results

By utilizing constitutively active and dominant negative RHOA, we show that RHOA negatively regulates both in vitro and in vivo migration and dominant negative RHOA significantly increased the migration potential of human HSC/HPCs. Active RHOA expression favors the retention of hematopoietic stem/progenitor cells in the niche rather than migration and was found to lock the cells in the G0 cell cycle phase thereby affecting their long-term self-renewal potential.

Conclusion

The current study demonstrates that down-regulation of RHOA might be used to facilitate the migration and homing of hematopoietic stem cells without affecting their long-term repopulating ability. This might be of interest especially for increasing the homing of ex vivo expanded HSPC.

【 授权许可】

   
2013 Jaganathan et al.; licensee BioMed Central Ltd.

【 图 表 】

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