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- Title
Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxia.
- Authors
Gharib, Sina A.; Khalyfa, Abdelnaby; Kucia, Magdalena J.; Dayyat, Ehab A.; Kim, Jinkwan; Clair, Heather B.; Gozal, David
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
PATHOPHYSIOLOGY of anoxemia; B cells; PLURIPOTENT stem cells; GENETIC transcription regulation; GENE expression; BONE marrow; RNA metabolism; BIOLOGICAL models; RESEARCH; CELL culture; ANIMAL experimentation; RESEARCH methodology; CELL physiology; EVALUATION research; MEDICAL cooperation; CELL motility; BIOINFORMATICS; COMPARATIVE studies; STEM cells; GENE expression profiling; GENES; GENOTYPES; RESEARCH funding; OLIGONUCLEOTIDE arrays; CHEMOKINES; MOLECULAR structure; HYPOXEMIA; PHENOTYPES; MICE
- Publication
Respiratory Research, 2011, Vol 12, Issue 5, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/1465-9921-12-63