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Evolution of regenerative mechanisms and stem cell systems

Researchers from around the world participated in the first annual symposium organised by the Centre for Organismal Studies (COS) Heidelberg in early July to discuss the evolution of the regenerative mechanisms and stem cell systems of plants and animals. Although stem cells and the multicellularity of animals and plants evolved independently from each other, their stem cell systems are nevertheless governed by the same principles.

The Centre for Organismal Studies (COS) Heidelberg was founded in 2010 as a result of the merger between the Institute of Zoology and the Institute of Plant Sciences with the objective of taking research into the basic processes of organismal life beyond the borders of traditional biological disciplines. In early July 2012, the Centre for Organismal Studies organised the first “COS Symposium”, which will now be held in Heidelberg every year. Researchers from Heidelberg and international speakers presented and discussed state-of-the-art research results relating to the basic molecular and cellular mechanisms that govern animals, plants and basal forms of life.

This year’s COS Symposium “At the roots of stemness” focused on the evolution of regenerative mechanisms and stem cell systems. Oral and poster presentations used a broad range of different model organisms to provide a “snapshot of the diversity of biological systems”, said Prof. Dr. Jochen Wittbrodt, Managing Director of COS, in his welcome address.

The symposium was made possible thanks to financial support from the non-profit Klaus Tschira Foundation, the Cooperative Research Centre 873 (“Self-Renewal and Differentiation of Stem Cells”) funded by the German Research Foundation (DFG) and the company Nikon, which runs the Nikon Imaging Centre at the University of Heidelberg BioQuant centre. The imaging centre works on the development of new microscopic methods.

Plants: Differentiation instead of dedifferentiation

Prof. Dr. Elliot Meyerowitz © CalTech

Many of the research results presented would not have been possible without the enormous progress made in the field of light microscopy. Professor Dr. Elliot Meyerowitz from the California Institute of Technology in Pasadena provided an impressive example of this progress in his keynote lecture, which dealt with the fate of plant stem cells during organ development and differentiation using genetically engineered fluorescent gene markers. The renowned American biologist and his team investigated callus cultures of the shoot meristem of Arabidopsis, a popular model plant amongst biologists. Professor Dr. Lohmann, Director of the Department of Stem Cell Biology at the COS, has also shown that the shoot meristem from which surface plant parts (shoot, leaves, blossoms) develop contains pluripotent stem cells that are embedded in a stem cell niche consisting of several hundreds of multipotent progenitor cells (see also article entitled “Regulatory networks of plant stem cell systems”). Pieces of plant tissue (shoot, roots, leaves or petals) of Arabidopsis and many other plants can be grown in a bioreactor into a colourless mass of cells (callus) and induced to differentiate (forming a shoot/root meristem and eventually an intact new plant) by supplementing the medium with plant growth regulators (e.g. auxin).

Freshwater polyp drawn by Abraham Trembley in 1744. © R. Hertwig & R. v. Wettstein 1914

The regenerative ability of plants has until now been regarded as evidence for the totipotency of living plant cells (in contrast to animal cells). However, the American researchers have been able to show with their gene marker constructs that a callus – no matter which organ it was derived from – does not represent an undifferentiated or dedifferentiated cell mass, but instead is highly organised and has the same gene expression pattern as certain stem cells of the root meristem (so-called xxp - xylem pole pericycle - cells). According to these findings, a callus does not grow from all cell populations of the starting tissue, but instead from adult stem cells with gene properties of xpp cells that are found around the vessels in all plant tissues. Meyerowitz believes that the regenerative ability of plant tissue pieces depends on the presence of such adult stem cells. It therefore appears that what was previously regarded as a dedifferentiation process is actually the differentiation of toti- or pluripotent stem cells.

Immortal cnidarians

Prof. Dr. Thomas W. Holstein, Director, Institute of Zoology, University of Heidelberg © University of Heidelberg

Professor Dr. Thomas Holstein from COS Heidelberg has found out that cnidarians such as the freshwater polyp Hydra and the sea anemone Nematostella have a regenerative ability that is similar to that of plants and is virtually unlimited. The organisms are also potentially immortal as a result of asexual reproduction. The incredible properties of multicellular animals (metazoans) were discovered by Abraham Trembley back in the 18th century in his world-famous experiments (see article entitled "The Hydra genome"). More than a hundred years ago, developmental biologists showed that the regenerative ability of freshwater polyps is down to so-called interstitial cells which are predominantly found around the polyp’s mouth, but which also have the ability to migrate around the entire organism. These cells are epithelial stem cells, which are located between the true epithelial cells. Holstein and his team have shown that these cells can differentiate into nerve, gland and stinging cells. Hydra germ cells are also derived from interstitial stem cells.

Holstein and his team have shown that many signalling cascades that control embryonic development and differentiation in higher animals are already present in much simpler freshwater polyps. These include the Wnt signalling pathway which is as complex in Hydra as it is in the developmental lineage that leads to humans (deuterostomes) but is much simpler in protostomes (such as threadworms, insects and molluscs). The proteins BMP (bone morphogenetic protein), notch and hedgehog, which are all morphogenetic tools of bilaterally symmetrical animals (bilaterians), are already present in the head area of Hydra and most likely responsible for the determination of the oral-aboral axis of actinomorphic (radially symmetrical) cnidarians. The researchers from Heidelberg, who have made considerable contributions to deciphering the Hydra genome, now use the genomic data in combination with novel functional and proteomic approaches for the detailed analysis of the regulatory network that governs the renewal of stem cells in Hydra. Holstein emphasised in his lecture that these results could lead to important findings relating to the basic mechanisms of stem cell biology and the roles played by external signals in determining the fate of individual cells and cell lines in tissue, cell ageing, reprogramming and differentiation.

The origin of multicellularity

Studies have shown that cnidarians separated from other metazoans prior to the origin of the bilaterian assemblage (i.e. the large taxonomic clades of protostomes and deuterostomes). At the COS Symposium, Dr. Bruce Edgar from the ZMBH-DKFZ Alliance and Professor Dr. Jochen Wittbrodt presented the stem cell systems of these animal groups. This will be dealt with elsewhere.

The chalk sponge Sycandra with a choanocyte layer. © Humboldt-University Berlin, Zoological Collection

Noriko Funayama from Kyoto University presented the stem cell systems of sponges (Spongi, Porifera), which are even more primitive than cnidarians. Sponges are the most simple multicellular animals on Earth; they do not possess true tissue and only consist of a few cell types. They have a virtually unlimited ability to regenerate, which is believed to be due to archaeocytes, unspecialised stem cells that are able to migrate in the extracellular jelly-like matrix (mesohyl) and transform into other cells. The expression of stem cell gene markers enabled Funayama and her team to show that archaeocytes have the ability to self-renew and generate progeny capable of differentiating into other cell types. The researchers also found that sponges possess choanocytes that express stem cell genes that are able to produce totipotent germ cells. Funayama believes that both cell types – archaeocytes and choanocytes – are pluripotent stem cells.

Choanocytes have a flagellum surrounded by a collar of microvilli. The flagellae beat and create a flow of water across the microvilli which filter nutrients (e.g. bacteria) from the water. Choanocytes are fairly similar to unicellular organisms known as choanoflagellates, to the extent that there is very little doubt about their relationship. There are also colony-forming choanoflagellates that look very much like sponges, which is why they were called Proterospongia. Their individual cells are embedded in a jelly-like matrix similar to the mesohyl of sponges. Moreover, they are used as models for showing how the stem cell system of multicellular animals might have evolved from unicellular organisms. 

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