Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem cells and activates developmental transcriptional programs in mice.

BACKGROUND: Obstructive sleep apnea is a prevalent disorder associated with cognitive dysfunction and cardiovascular and metabolic morbidity and is characterized by recurrent episodes of hypoxia during sleep. Bone marrow-derived very small embryonic-like (VSEL) pluripotent stem cells represent a rec...

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Publicado en:Sleep Vol. 33; no. 11; pp. 1439 - 1447
Autores principales: Gharib SA, Dayyat EA, Khalyfa A, Kim J, Clair HB, Kucia M, Gozal D
Formato: research Journal Article
Publicado: Oxford University Press / USA 2010 Nov 1
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2010 Nov 1
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      pub: Oxford University Press / USA
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        atl: Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem cells and activates developmental transcriptional programs in mice.
      aug:
        au:
          Gharib SA
          Dayyat EA
          Khalyfa A
          Kim J
          Clair HB
          Kucia M
          Gozal D
      sug:
        subj:
          Anoxia Blood
          Bone Marrow Metabolism
          Molecular Structure
          Stem Cells Metabolism
          Animal Studies
          Anoxia Physiopathology
          Biological Markers Blood
          Chemokines Blood
          Cytokines Blood
          Factor Analysis
          Flow Cytometry Methods
          Genes
          Hematopoietic Stem Cells Metabolism
          Male
          Mice
          Microarray Analysis Methods
          Models, Biological
          Male
      ab: BACKGROUND: Obstructive sleep apnea is a prevalent disorder associated with cognitive dysfunction and cardiovascular and metabolic morbidity and is characterized by recurrent episodes of hypoxia during sleep. Bone marrow-derived very small embryonic-like (VSEL) pluripotent stem cells represent a recruitable pool that may play an important role in organ repair after injury. We hypothesized that exposure to intermittent hypoxia (IH) can mobilize VSELs from the bone marrow (BM) to peripheral blood (PB) in mice and can activate distinct transcriptional programs. METHODS: Adult mice were exposed to IH or normoxia for 48 hours. VSELs were sorted from BM and PB using flow cytometry. Plasma levels of stem cell chemokines, stromal cell derived factor-1 (SDF-1), hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) were measured. Transcriptional profiling of VSELs was performed, and differentially expressed genes were mapped to enriched functional categories and genetic networks. RESULTS: Exposure to IH elicited migration of VSELs from BM to PB and elevations in plasma levels of chemokines. More than 1100 unique genes were differentially expressed in VSELs in response to IH. Gene Ontology and network analysis revealed the activation of organ-specific developmental programs among these genes. CONCLUSIONS: Exposure to IH mobilizes VSELs from the BM to PB and activates distinct transcriptional programs in VSELs that are enriched in developmental pathways, including central nervous system development and angiogenesis. Thus, VSELs may serve as a reserve mobile pool of pluripotent stem cells that can be recruited into PB and may play an important role in promoting end-organ repair during IH. CITATION: Gharib SA; Dayyat EA; Khalyfa A; Kim J; Clair HB; Kucia M; Gozal D. Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem cells and activates developmental transcriptional programs in mice. SLEEP 2010;33(11):1439-1446.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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