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PMID: 21102985 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Sleep ·Vol. 33 ·No. 11 ·2010-11-00 ·Pages 1439-46

Gharib SA, Dayyat EA, Khalyfa A, Kim J, Clair HB, Kucia M, Gozal D

Abstract

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. 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. 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. 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.

Keywords
Stem cells intermittent hypoxia sleep apnea
MeSH Terms
Animals Biomarkers/blood Bone Marrow Cells/metabolism Chemokine CXCL12/blood Chemokines/blood Disease Models, Animal Embryonic Stem Cells/metabolism Flow Cytometry/methods Gene Expression Regulation Gene Regulatory Networks Hematopoietic Stem Cells/metabolism Hepatocyte Growth Factor/blood Hypoxia/blood,physiopathology Leukemia Inhibitory Factor/blood Male Mice Mice, Inbred C57BL Microarray Analysis/methods Principal Component Analysis
Chemicals
Biomarkers Chemokine CXCL12 Chemokines Leukemia Inhibitory Factor Hepatocyte Growth Factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gharib Sina A
Center for Lung Biology and UW Medicine Sleep Instiute, Department of Medicine, University of Washington, WA, USA.
Dayyat Ehab A
Khalyfa Abdelnaby
Kim Jinkwan
Clair Heather B
Kucia Magdalena
Gozal David
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Article Info
Journal
Sleep
Abbr.
Sleep
ISSN
0161-8105
DOI
10.1093/sleep/33.11.1439
Published
2010-11-00
Pages
1439-46
Language
English
Region
United States
NLM ID
7809084
PMCID
PMC2954693
Subset
IM
Grants
NHLBI NIH HHS · R01 HL065270 · United States
NHLBI NIH HHS · R01 HL086662 · United States
NHLBI NIH HHS · HL086662 · United States
NHLBI NIH HHS · HL065270 · United States
External Links
PubMed source DOI: 10.1093/sleep/33.11.1439 PMC Full Text View journal details
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