June 9, 2009 How can stem cells be used in regenerative medicine? In what way might they lead to certain cancers? Stem cell research is a major challenge for medicine. Recently, asymmetric cell division was filmed in vivo in fruit fly germinal stem cells for the first time by the team of Jean-René Huynh at the Institut Jacques Monod (CNRS/Université Paris Diderot), now working at the ‘Génétique du développement et cancer' laboratory (Institut Curie/CNRS/UPMC/Inserm). This new step towards our understanding of stem cell behavior is published in Nature Cell Biology.
As stem cells can produce any kind of cells in higher animals, they are a crucial focus of research interest. On one hand, these unspecialized cells are self-renewing, producing identical duplicates. On the other hand, they are capable of producing one or more specialized cell types in an organism: gametes, skin, liver, etc. In view of these capacities, the team of CNRS researcher Jean-René Huynh is attempting to understand this regenerative capacity. How do stem cells, while dividing a great many times, manage to maintain their growth rate and size while producing daughter cells capable of differentiating and forming different organs?
Huynh and his team have worked on germline stem cells *(1)* of the fruit fly /Drosophila/, an insect whose simplicity, genetics and rapid life cycle have made it a model species. For the first time they filmed germline stem cells dividing /in vivo/ in their cellular environment(using fluorescent markers). It hasn't yet been possible to view vertebrate cells /in /vivo and such studies are usually made on cultured cells.
The researchers identified a new gene needed for the growth and multiplication of stem cells, which they have named /wicked/. By characterizing the biochemical function of the protein coded by the /wicked /gene (Wicked protein) the researchers showed that it was used to make ribosomes *(2)*, necessary for protein production and cellular growth. By filming the germline stem cells /in vivo/, they saw that the Wicked protein was located asymmetrically. At the end of the division there are no Wicked/ /proteins in the stem cell, except in the daughter cell that will differentiate into a gamete.
The researchers have also proven that the asymmetric localization phenomenon is not only in the germline. Neural stem cells, which give rise to thousands of adult brain neurons, also preferentially accumulate the Wicked protein. When their /wicked/ gene has a dysfunctional mutation, these stem cells become smaller and produce fewer neurons.
The team's results reveal that a preferential accumulation of ribosomal biogenesis components (related to accumulation of the Wicked protein) is a possible mechanism leading to asymmetrical cellular growth. The adaptation of an ordinary cellular process can therefore explain some of the exceptional capacities of these stem cells. By improving our understanding of fundamental stem cell biology we can envisage their use in regenerative medicine, to repair malformed, damaged or aging tissues. Additionally, by understanding the regulation of stem cell multiplication, scientists could find ways of explaining the reasons for certain cancers occurring when the capacity for cellular multiplication is unregulated, and which are incurable using normal treatments.
(1)* Germinal stem cells are cells destined to multiply and differentiate into gametes.
(2)* Ribosomes are ribonucleoprotein molecules that play a role in cellular protein synthesis by decoding the information in messenger RNA.
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- Pierre Fichelson, Clara Moch, Kenzo Ivanovitch, Charlotte Martin, Clara M Sidor, Jean-Antoine Lepesant, Yohanns Bellaiche & Jean-Rene Huynh. Live-imaging of single stem cells within their niche reveals that a U3snoRNP component segregates asymmetrically and is required for self-renewal in Drosophila. Nature Cell Biology, 2009; 11 (6): 685 DOI: 10.1038/ncb1874
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