Bromodeoxyuridine induces senescence in neural stem and progenitor cells

Ross, Heather H., Levkoff, Lindsay H., Marshall II, Gregory P., Caldeira, Maria, Steindler, Dennis A., Reynolds, Brent A. and Laywell, Eric D. (2008) Bromodeoxyuridine induces senescence in neural stem and progenitor cells. Stem cells, 26 12: 3218-3227. doi:10.1634/stemcells.2008-0299

Author Ross, Heather H.
Levkoff, Lindsay H.
Marshall II, Gregory P.
Caldeira, Maria
Steindler, Dennis A.
Reynolds, Brent A.
Laywell, Eric D.
Title Bromodeoxyuridine induces senescence in neural stem and progenitor cells
Journal name Stem cells   Check publisher's open access policy
ISSN 1066-5099
Publication date 2008-12-01
Sub-type Article (original research)
DOI 10.1634/stemcells.2008-0299
Volume 26
Issue 12
Start page 3218
End page 3227
Total pages 10
Place of publication Durham, NC.
Publisher Wiley-Blackwell and AlphaMed Press
Language eng
Subject 06 Biological Sciences
10 Technology
11 Medical and Health Sciences
1103 Clinical Sciences
Abstract Bromodeoxyuridine (BrdU) is a halogenated pyrimidine that incorporates into newly synthesized DNA during the S phase. BrdU is used ubiquitously in cell birthdating studies and as a means of measuring the proliferative index of various cell populations. In the absence of secondary stressors, BrdU is thought to incorporate relatively benignly into replicating DNA chains. However, we report here that a single, low-dose pulse of BrdU exerts a profound and sustained antiproliferative effect in cultured murine stem and progenitor cells. This is accompanied by altered terminal differentiation, cell morphology, and protein expression consistent with the induction of senescence. There is no evidence of a significant increase in spontaneous cell death; however, cells are rendered resistant to chemically induced apoptosis. Finally, we show that a brief in vivo BrdU regimen reduces the proliferative potential of subsequently isolated subependymal zone neurosphere-forming cells. We conclude, therefore, that BrdU treatment induces a senescence pathway that causes a progressive decline in the replication of rapidly dividing stem/progenitor cells, suggesting a novel and uncharacterized effect of BrdU. This finding is significant in that BrdU-incorporating neural stem/progenitor cells and their progeny should not be expected to behave normally with respect to proliferative potential and downstream functional parameters. This effect highlights the need for caution when results based on long-term BrdU tracking over multiple rounds of replication are interpreted. Conversely, the reliable induction of senescence in stem/progenitor cells in vitro and in vivo may yield a novel platform for molecular studies designed to address multiple aspects of aging and neurogenesis. Disclosure of potential conflicts of interest is found at the end of this article.
Keyword Neurosphere
Neural stem cell
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 18 May 2010, 22:59:04 EST by Laura McTaggart on behalf of Queensland Brain Institute