title: Active RHOA favors retention of human hematopoietic stem/progenitor cells in their niche.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. bithiahgj@iitg.ernet.in.
authors.forename: Bithiah Grace
authors.initials: BG
authors.lastname: Jaganathan
authors.forename: Fernando
authors.initials: F
authors.lastname: Anjos-Afonso
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005312:Fetal Blood / Q000378:metabolism; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D060888:Real-Time Polymerase Chain Reaction; D020742:rhoA GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein
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