Stem cell regulation in a marine annelid

Whereas regeneration in mammals is restricted to few tissues, many invertebrates possess remarkable regeneration capacity that even includes the central nervous system. This capacity has been linked to the presence of specific cells that are characterized by a molecular fingerprint related to germ line cells. It has been speculated that this molecular fingerprint endows cells with stem cell abilities. But research into these cells has so far been limited to very few model species. The marine bristleworm Platynereis is a highly attractive organism for regeneration and stem cell research. Not only does this animal regenerate its trunk (including a functional central nervous system) after amputation. But in addition, the regeneration capacity of this worm is under tight control by a brain hormone activity that has long remained enigmatic. One intriguing possibility therefore is that the bristleworm possesses stem cells that are under hormonal control. Studies by one of the participating research groups have indeed identified cells in the regenerating tissue that are designated by the molecular fingerprint that makes them strong candidates for multipotent stem cells. Moreover, the second participating research group has recently identified the first bioactive component of the long-sought brain hormone activity. These complementary studies by both research teams will now allow them to engage in a highly synergistic project and answer two fundamental questions that are of key relevance for understanding the bristleworms fantastic regenerative system: a) Are the identified special cells indeed stem cells, i.e. are they able to self-renew and directly contribute to the regrowing tissue? b) Does the brain as well as the identified brain hormone component influence these cells, either on the molecular level, or in their ability to perform their functions? The answers to these questions will enable the team to gain critical insight into the mechanisms of stem cells and their hormonal control, and thereby break new scientific grounds in stem cell research.

The international research project "Stem cell regulation in a marine annelid" has yielded novel insight into the ways how brain-derived hormones can influence the regrowth of body parts. Stem cells play major roles in development and disease. Apart from their role in regular developmental growth, stem cells also allow certain animals to regenerate lost tissue. Regenerative capacities, however, differ greatly between species, raising questions as to what defines such capacities. Research into the regulation of stem cells in the context of regenerative growth therefore holds potential to unravel existing underlying regulatory processes. The international research project has investigated a potential role of hormones in regulating stem cells in regenerative growth. It has taken advantage of a marine annelid worm whose regeneration capacity dramatically changes under the influence of brain-derived hormones. The experimental research performed in the context of the project were aimed at characterizing the molecular makeup of the stem cell system involved in regenerative growth, to visualize such cells in the animal, and to assess if or not there were changes in the cellular signatures when the animals were deprived of hormones. In a collaborative effort, the involved teams approached these questions from different directions: by analyzing cellular proliferation and the expression of established marker genes under different hormonal situations, by establishing a method for dissociating regenerating tissue and characterizing the molecular "signatures" of thousands of individual cells ("single-cell sequencing"), and by introducing stable fluorescent biomarkers into animals prior to regeneration, in order to map the tissue source of the regenerating cells. The project has contributed to a series of scientific publications. The work of the Austrian team has also allowed the development of a new technique (DEEP-Clear) for visualizing cells, cellular markers or entire nervous systems in the context of whole organisms that was found to be broadly applicable to other species, ranging from squids to salamanders. Altogether, the project has yielded both scientific insight and technological advance that will be relevant for future analyses of animal stem cell systems and their regulation.