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).
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 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, 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.
Illustration: Ovariole of Drosophila melanogaster. (The organ where gametes form in insects). Germinal stem cells are at the extreme rear. DNA is shown in blue. (Magnification 630x) –
Copyright Jean-René Huynh.
Centre National de la Recherche Scientifique News Release (06/02/09)
Alpha Galileo News Release (06/05/09)
Science Daily (06/09/09)
Abstract (Nature Cell Biology; 11, 685-693 (05/10/09))