title: Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxia.
abstract: BACKGROUND
  Hypoxia is a ubiquitous feature of many lung diseases and elicits cell-specific responses. While the effects of hypoxia on stem cells have been examined under in vitro conditions, the consequences of in vivo oxygen deprivation have not been studied.
  
  
  METHODS
  We investigated the effects of in vivo hypoxia on a recently characterized population of pluripotent stem cells known as very small embryonic-like stem cells (VSELs) by whole-genome expression profiling and measuring peripheral blood stem cell chemokine levels.
  
  
  RESULTS
  We found that exposure to hypoxia in mice mobilized VSELs from the bone marrow to peripheral blood, and induced a distinct genome-wide transcriptional signature. Applying a computationally-intensive methodology, we identified a hypoxia-induced gene interaction network that was functionally enriched in a diverse array of programs including organ-specific development, stress response, and wound repair. Topographic analysis of the network highlighted a number of densely connected hubs that may represent key controllers of stem cell response during hypoxia and, therefore, serve as putative targets for altering the pathophysiologic consequences of hypoxic burden.
  
  
  CONCLUSIONS
  A brief exposure to hypoxia recruits pluripotent stem cells to the peripheral circulation and actives diverse transcriptional programs that are orchestrated by a selective number of key genes.
authors.affiliation: Center for Lung Biology and Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Kucia
authors.forename: Ehab A
authors.initials: EA
authors.lastname: Dayyat
authors.forename: Jinkwan
authors.initials: J
authors.lastname: Kim
authors.forename: Heather B
authors.initials: HB
authors.lastname: Clair
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D048430:Cell Shape; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood; D019295:Computational Biology; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005838:Genotype; D000860:Hypoxia / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D018925:Chemokines; D012333:RNA, Messenger