Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxiaReportar como inadecuado

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Respiratory Research

, 12:63

First Online: 01 December 2011Received: 11 February 2011Accepted: 10 May 2011


BackgroundHypoxia 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.

MethodsWe 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.

ResultsWe 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.

ConclusionsA 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-63 contains supplementary material, which is available to authorized users.

Sina A Gharib, Abdelnaby Khalyfa contributed equally to this work.

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Autor: Sina A Gharib - Abdelnaby Khalyfa - Magdalena J Kucia - Ehab A Dayyat - Jinkwan Kim - Heather B Clair - David Gozal


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