Group 4 - Current and future directions for stem cell science

Chair: Professor Patrick Tam

The conceptual paradigm of stem cell biology is founded on discoveries on the process of cell lineage differentiation in development, tissue homeostasis and cancer cell biology. In the embryo, populations of cells that exist transiently during development have been shown to be able to generate a wide range (and potentially all) of the cell types present in the adult organism. In the mature tissues that are constantly replenished during life, such as the gut epithelium, blood cells and the skin, or can launch repair and healing of damages, such as the liver and muscles, self-renewing cell populations with multi-lineage potency that act as the precursors of the tissue-specific cell types have been identified. Collectively these are known as adult (tissue) stem cells; the best studied among them are the haematopoietic stem cells, the intestinal stem cells and the skin stem cells. Putative stem cells have also been identified in embryonal carcinoma, where it has been demonstrated experimentally a single embryonic carcinoma cells can differentiate into the diverse types of tissues found in a teratocarcinoma. Research in stem cell biology has been escalated by the accomplishment of capturing stem cells from the developing embryo of the mouse and the human. That these cells can be maintained in vitro as eternally self-renewing pluripotent cell lines enables direct experimental manipulation and performance of multifaceted analysis of their stemness, lineage potency and functional attributes of differentiation. The seminal discovery of that terminally differentiated somatic cells can be reprogrammed to become pluripotent stem cells that are similar to the embryonic stem cells has led to another quantum leap in the scope of research endeavour in stem cell biology.

Current research in stem cell biology can be broadly delineated into:

• identification and characterisation of the resident stem cells and their niche in embryos and adult tissues, and their role in development and tissue homoeostasis/regeneration in model organisms
• study of human and animal development in patterned and three-dimensional in vitro differentiation models of pluripotent stem cells
• establishment, maintenance and transition of the stem cell state of embryonic, adult and induced pluripotent stem cells and the consequential functional attributes.
• the differentiation potential of stem cells: lineage propensity and options.
• Characterisation of the roadmap and signposts of lineage differentiation of stem cells: cell biology and    ̴omics insights of in vitro directed differentiation and parallel proceedings in vivo.
• Mechanism, pathway and endpoints of cellular reprogramming to pluripotency and the acquisition of ‘synthetic’ cell fate through targeted reprogramming or trans-differentiation.
• Translation of the stem cell knowledge to application in medicine, drug research and biotechnology.

The first task of this discussion group is to take a snapshot of the advances that have been achieved in these research domains, the ongoing research endeavour and the likely outcome, and to reflect on how stem cell research in Australia is tracking and to take stock of what we have or would have accomplished in the context of the international effort and contribution.

Questions to get you thinking:

1. Are there any doors that are yet to be opened in these research domains?
2. Could we forecast any new paradigm of stem cell research that may evolve from the current domains or through the multi-domain integration of knowledge and research expertise?
3. Are there any research domains that align well with our goal and priority, and the national interest?
4. How are we going to position our research workforce to engage the future scientific endeavour in stem cell biology by, e.g. building expertise, establishing infrastructure and enhancing the research environment?

References and reading material

Stem Cell Australia: 2014 Annual Report:  http://www.stemcellsaustralia.edu.au/News---Events/News/Stem-Cells-Australia-2014-Annual-Report-now-available.aspx

Kobold S, Guhr A, Kurtz A and Loser P. (2015) ‘Human embryonic and induced pluripotent stem cell research trends: Complementation and diversification of the field’. Stem Cell Reports 4(5):914-925. http://www.cell.com/stem-cell-reports/abstract/S2213-6711(15)00096-X

Hussein SMI et al. (2014) ‘Genome-wide characterization of the route to pluripotency’. Nature 516: 198-206. http://www.nature.com/nature/journal/v516/n7530/full/nature14046.html

Ben-Zvi D and Melton DA (2015) ‘Modeling human nutrition using human embryonic stem cells’. Cell 161(1):12-17. http://www.cell.com/cell/abstract/S0092-8674(15)00240-8