Important transcription factors that can induce and preserve pluripotency were discovered in the course of this research. So what can planarians contribute to the current research if their stem cells cannot be cultivated and reproduced outside of the body?
This is precisely where the strength of the planarians as a model system in stem cell research lies: the combination they can offer of a natural extracellular environment and pluripotent stem cells. Whereas cultivated stem cells are normally taken out of their natural environment and all important interactions with neighbouring cells and freely moving molecules are interrupted as a result, the stem cells in planarians can be observed and manipulated under normal conditions in vivo.
Although planarians have been renowned as masters of regeneration and research objects for generations, they have undergone a genuine explosion in research interest in recent years. In particular, the possibility of switching off specific genes through RNA interference RNAi and the availability of the genome sequence of Schmidtea mediterranea , a planarian species which is especially good at regenerating itself, have contributed to this surge in interest.
Hence, it is possible to examine which messenger RNAs mRNAs are produced that act as molecular templates for the production of proteins. However, the real work only starts here: the extent to which the presence of a particular mRNA also reflects the volume of protein that is active in the cell remains to be determined. It is mainly the proteins in the form of enzymes, signalling molecules and structural elements, and not their mRNAs, that ultimately control the majority of cellular processes.
In addition, their production using mRNA templates and their lifetime are precisely regulated processes and the frequency with which an mRNA arises cannot provide any information about these processes. The time has come, therefore, to develop experimental approaches for planarians that extend beyond gene expression analysis and lend greater significance to the subsequent regulatory processes.
Combined with the marking of proteins, quantitative mass spectrometry, which enables the identification of thousands of protein fragments based on their mass, provides a starting point here. The natural amino acid lysine, for example, contains six carbon atoms, each of which has six neutrons and six protons 12 C6 lysine. This enables the direct comparison of the abundance of a particular protein present in marked and non-marked samples.
Over 96 percent labelling efficiency which corresponds to the degree of labelling of the SILAC mouse liver was attained after fewer than 20 weeks. To mark their proteins with heavy amino acids, the worms were presented with liver from SILAC mice [5], which they consumed with relish and without suffering any side effects.
Consequently, with the help of the SILAC method, the lifetime of a protein can be estimated and protein volumes can be compared at different times and in different tissues. To specifically identify the proteins that accumulate in the stem cells of the planarians, the frequency of the proteins in stem cells and in already specialised cells was measured and compared.
They included numerous proteins that arise in a similar form in other organisms and their stem cells, and had been linked with various processes, for example the control of chromatin structure, gene expression and metabolism.
An astonishing proportion of these proteins - over one third - could have something to do with the regulation of protein production itself, and this would suggest that the volume of mRNA does not actually reflect the number of the associated proteins [6].
The targeted deactivation of Ncoa5 — a nuclear protein that can control the activation of genes — using RNAi causes serious regeneration defects A and stem cell loss B. While there are many differences between the stem cells of mice and those of planarians, they also have things in common. A nuclear protein was actually found in the SILAC proteome that had not been directly linked with stem cells before.
This protein, which is known as nuclear receptor co-activator 5 Ncoa5 , belongs to the family of proteins that can control the activation of genes and therefore convert the orders that a cell receives from the extracellular environment into reactions. A change in the gene expression can have serious consequences for the cell and, for example, make a specialised muscle or nerve cell out of a pluripotent cell.
The targeted deactivation of Ncoa5 with RNAi actually caused serious regeneration defects and the planarians lost all of their stem cells in a matter of a few weeks. Interestingly, the activation of Ncoa5 expression in the pluripotent cells of the early mouse embryo could be detected in experiments on mouse embryos Fig. Further research is currently being carried out to determine the mechanism whereby Ncoa5 contributes to the preservation of the presence of stem cells in planarians and whether its counterpart in the mouse is also necessary to for the preservation of pluripotency.
Despite the rapid progress being made, the technologies for researching the planarian stem cells and their self-preservation mechanisms are still in their infancy.
Save my name, email, and website in this browser for the next time I comment. Toggle navigation. Home Research Planarians…the key to regenerative med Though the road will be a long one, such scientific effort will hopefully one day teach us how to make organs in the lab, and make regenerative medicine a reality… Picture credits: Lin, A. Report post. Leave a Reply Cancel reply Your email address will not be published.
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Contact us Do you have a question or suggestion for the Node? Anything scientists learn about regeneration by studying a relatively simple creature, like a planarian, can hold important clues into how they could one day coax human cells to behave similarly and help humans regenerate injured or missing tissues.
Molly Torinus 9. Could we use planarians to help us understand human regeneration? Melanie Issigonis.
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