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Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile

Leonardo Rossi1*, Alessandra Salvetti1, Francesco M Marincola2, Annalisa Lena1, Paolo Deri3, Linda Mannini3, Renata Batistoni3, Ena Wang2 and Vittorio Gremigni1

Author Affiliations

1 Dipartimento di Morfologia Umana e Biologia Applicata, Sezione di Biologia e Genetica, Università di Pisa, Via Volta, Pisa 56126, Italy

2 Department of Transfusion Medicine, Warren G Magnuson Clinical Center, National Institutes of Health, Central Drive, Bethesda, Maryland 20892, USA

3 Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università di Pisa, Via Carducci, Pisa 56010, Italy

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Genome Biology 2007, 8:R62  doi:10.1186/gb-2007-8-4-r62

Published: 20 April 2007

Abstract

Background

Mammalian stem cells are difficult to access experimentally; model systems that can regenerate offer an alternative way to characterize stem cell related genes. Planarian regeneration depends on adult pluripotent stem cells - the neoblasts. These cells can be selectively destroyed using X-rays, enabling comparison of organisms lacking stem cells with wild-type worms.

Results

Using a genomic approach we produced an oligonucleotide microarray chip (the Dj600 chip), which was designed using selected planarian gene sequences. Using this chip, we compared planarians treated with high doses of X-rays (which eliminates all neoblasts) with wild-type worms, which led to identification of a set of putatively neoblast-restricted genes. Most of these genes are involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are pivotal in neoblast regulation. Comparing planarians treated with low doses of X-rays (after which some radiotolerant neoblasts re-populate the planarian body) with specimens irradiated with high doses and unirradiated control worms, we identified a group of genes that were upregulated as a consequence of low-dose X-ray treatment. Most of these genes encode proteins that are known to regulate the balance between death and survival of the cell; our results thus suggest that genetic programs that control neoblast cytoprotection, proliferation, and migration are activated by low-dose X-rays.

Conclusion

The broad differentiation potential of planarian neoblasts is unparalleled by any adult stem cells in the animal kingdom. In addition to our validation of the Dj600 chip as a valuable platform, our work contributes to elucidating the molecular mechanisms that regulate the self-renewal and differentiation of neoblasts.