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Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxia

Sina A Gharib1, Abdelnaby Khalyfa23, Magdalena J Kucia4, Ehab A Dayyat2, Jinkwan Kim23, Heather B Clair2 and David Gozal23*

Author Affiliations

1 Center for Lung Biology and Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA, USA

2 Department of Pediatrics, University of Louisville, Louisville, KY, USA

3 Department of Pediatrics, University of Chicago, Chicago, IL, USA

4 Stem Cell Biology Institute, University of Louisville, Louisville, KY, USA

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Respiratory Research 2011, 12:63  doi:10.1186/1465-9921-12-63

Published: 10 May 2011

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.