title: Cholesterol synthesis-related enzyme oxidosqualene cyclase is required to maintain self-renewal in primary erythroid progenitors.
abstract: OBJECTIVE
  Molecular mechanisms controlling cell fate decision making in self-renewing cells are poorly understood. A previous transcriptomic study, carried out in primary avian erythroid progenitor cells (T2ECs), revealed that the gene encoding oxidosqualene cyclase (OSC/LSS), an enzyme involved in cholesterol biosynthesis, is significantly up-regulated in self-renewing cells. The aim of the present work is to understand whether this up-regulation is required for self-renewal maintenance and what are the mechanisms involved.
  
  
  METHODS
  To investigate OSC function, we studied effects of its enzymatic activity inhibition using Ro48-8071, a specific OSC inhibitor. In addition, we completed this pharmacological approach by RNAi-mediated OSC/LSS knockdown. The study of OSC inhibition was carried out on both self-renewing and differentiating cells to observe any state-dependent effect.
  
  
  RESULTS
  Our data show that OSC acts both by protecting self-renewing T2EC cells from apoptosis and by blocking their differentiation program, as OSC inhibition is sufficient to trigger spontaneous commitment of self-renewing cells towards an early differentiation state. This is self-renewal specific, as OSC inhibition has no effect on erythroid progenitors that have already differentiated.
  
  
  CONCLUSIONS
  Taken together, our results suggest that OSC/LSS expression and activity are required to maintain cell self-renewal and may be involved in the self-renewal versus differentiation/apoptosis decision making, by keeping cells in a self-renewal state.
authors.affiliation: Bases Moléculaires de l'Autorenouvellement et de ses Altérations" Group, Université de Lyon, Université Lyon 1, Villeurbanne, Centre de Génétique Moléculaire et Cellulaire, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Mejia-Pous
authors.forename: F
authors.initials: F
authors.lastname: Damiola
authors.forename: O
authors.initials: O
authors.lastname: Gandrillon
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001577:Benzophenones / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D002784:Cholesterol / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D006706:Homeostasis; D066298:In Vitro Techniques; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: D001577:Benzophenones; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; C105726:Ro 48-8071; D002784:Cholesterol; D019751:Intramolecular Transferases; C021924:lanosterol synthase