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


CONCLUSIONS
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.
Rossi
Leonardo
L
Dipartimento di Morfologia Umana e Biologia Applicata, Sezione di Biologia e Genetica, Università di Pisa, Pisa, Italy. leoros@biomed.unipi.it
Salvetti
Alessandra
A
Marincola
Francesco M
FM
Lena
Annalisa
A
Deri
Paolo
P
Mannini
Linda
L
Batistoni
Renata
R
Wang
Ena
E
Gremigni
Vittorio
V
D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010932:Planarians / Q000166:cytology / Q000235:genetics* / Q000528:radiation effects; D012313:RNA / Q000378:metabolism; D012038:Regeneration / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D014965:X-Rays
D012313:RNA