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Australian Biochemist the Magazine of the Australian Society for Biochemistry and Molecular Biology Inc ISSN 1443-0193 Australian Biochemist The Magazine of the Australian Society for Biochemistry and Molecular Biology Inc. Volume 47 APRIL 2016 No.1 SHOWCASE ON RESEARCH Stem Cells in Development and Cancer THIS ISSUE INCLUDES Showcase on Research Regular Departments Haematopoietic Stem Cells SDS (Students) Page Repairing the Damaged Heart Competition with Cardiac Progenitor Cells Sydney Protein Group SIG Defining Prostate Stem Cells Our Sustaining Members Generating Kidney Tissue Forthcoming Meetings from Pluripotent Stem Cells Directory INSIDE Profiles of ASBMB Medallists and Awardees Vol 47 No 1 April 2016 AUSTRALIAN BIOCHEMIST Page 1 ‘Lemberg Medal’ Competition We have another competition for the readers of the Australian Biochemist. All correct entries received by the Editor (email [email protected]) before 16 May 2016 will enter the draw to receive a gift voucher. With thanks to Rebecca Lew. Fill in the blanks around the letters in the words LEMBERG MEDAL with the names of previous medallists. L E M B E R G M E D A L The Australian Academy of Science Awards for 2017 are now open Please note that the closing date for nominations for honorific awards is 30 April 2016 and that nominations/ applications for research conferences, research awards and travelling fellowships are due by 15 June 2016. Nomination schemes and awards that may be of particular interest to you are also highlighted below: Gottschalk Medal (biomedical sciences) Nancy Millis Medal for Women in Science (any branch of the natural sciences) Ruth Stephens Gani Medal (human genetics including clinical, molecular, population and epidemiological genetics and cytogenetics) Gustav Nossal Medal (global health) Jacques Miller Medal (experimental biomedicine) Boden Research Conferences The Moran Award for history of science research Oxford Nuffield Medical Fellowship Selby Travelling Fellowship (all fields of science) Further information on the awards (including eligibility criteria and nomination/application procedures and forms) visit the website: www.science.org.au/awards or email: Dominic Burton (Awards Officer) [email protected] Page 2 AUSTRALIAN BIOCHEMIST Vol 47 No 1 April 2016 SHOWCASE ON RESEARCH EDITORIAL Stem Cells - What Makes Them Special? Stem cell biology is a rapidly moving field with transplantation and to expand blood stem cells ex vivo. profound implications for regenerative medicine and In their review of cardiac progenitor cells, Le and cancer. Stem cells can be broadly divided into two Chong show that the isolation and characterisation groups: 1. embryonic stem (ES) cells, which include of stem and progenitor cells in the normal heart is induced pluripotent stem cells (iPSC), and 2. tissue- crucial for developing strategies to replenish damaged specific stem cells (adult stem cells). The hallmark cardiac cells. Cardiovascular disease remains a major feature of stem cells is extensive self-renewal capacity. cause of morbidity worldwide. While it is still unclear ES cells are undifferentiated, pluripotent cells that can if implantation of progenitor cells into injured hearts give rise to every type of cell in the body. After birth, leads to myocardial repair by direct or indirect means, distinct populations of adult stem cells (very small in the delineation of paracrine signalling pathways number) are found in most organs and cellular systems. that influence the growth of these cells following In contrast to ES cells, adult stem cells are multipotent, transplantation remains an important area of research. as the differentiation capacity of these cells is limited In the third article, Taylor describes stem and to the organ or tissue in which they reside. These progenitor cells in prostate tissue and emphasises the tissue-specific stem cells maintain tissue homeostasis importance of dissecting heterogeneity to understand and repair damaged cells throughout the life of the the cell populations that drive prostate tumour growth. individual. Cell fate choices must be tightly regulated to Identification of ‘cells of origin of cancer’ may reveal ensure the correct supply of mature cells, otherwise cell biomarkers for prognosis and improved treatment. transformation and carcinogenesis can result. Questions Future challenges include the identification of cancer of paramount importance in stem cell biology are: 1. how stem cell populations that drive tumour growth and can we use our knowledge of normal tissue to identify eradication of regenerating tumour cells that are better markers and therapies for cancer patients, and 2. resistant to hormonal therapy. how can one harness the regenerative potential of stem The discovery that a fully mature, specialised somatic cells to replace diseased or damaged tissue? cell could be induced to mimic embryonic stem cells This issue of the Australian Biochemist features four under appropriate conditions has opened a new field articles from leading Australian stem cell researchers. of iPSC biology. In the fourth review, Little explores In the first, Ng and Alexander provide an overview the recent advances in regenerating kidney tissue from of haematopoietic stem cells. For more than 50 years, pluripotent stem cells. Kidney organoids can now be the haematopoietic system has paved the way for formed ex vivo after directed differentiation of human understanding stem cells and lineage hierarchies iPSCs. These and other redirected iPSCs have important and for deciphering the cellular constituents of solid implications for disease modelling and patient-specific organs. Blood stem cells, although very rare, are drug screening to identify better druggable targets. The capable of sustaining haematopoiesis in bone marrow next era remains a very exciting one for Australian stem transplantation owing to their robust self-renewing cell biologists seeking to build on their past discoveries potential. Future efforts are focussed on advancing stem and implement improvements in clinical practice through cell transplantation therapy to enable efficient allogeneic tissue regeneration and novel therapeutic targets in cancer. Jane Visvader Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052 [email protected] Cover Illustration Stem Cells in Development and Cancer A kidney organoid generated from Guest Editor: Jane Visvader a human pluripotent stem cell line (16). This organoid has been cultured 4 Haematopoietic Stem Cells for 18 days as an aggregate post- Ashley Ng and Warren Alexander induction of intermediate mesoderm. 7 Repairing the Damaged Heart with Cardiac Progenitor Cells Immunofluroescence displays the Thi Y.L. Le and James J.H. Chong presence of differentiating nephrons 10 Defining Prostate Stem Cells: Clues to Improving Prostate comprised of glomeruli (NPHS1, yellow), Cancer Treatment proximal tubules (LTL, pink) and distal Renea Taylor tubules/collecting ducts (CDH1, green). 13 Generating Kidney Tissue from Pluripotent Stem Cells Image courtesy of Dr Minoru Takasato Melissa Little (Murdoch Childrens Research Institute ). Australian Biochemist – Editor Chu Kong Liew, Editorial Officer Liana Friedman © 2016 Australian Society for Biochemistry and Molecular Biology Inc. All rights reserved. Vol 47 No 1 April 2016 AUSTRALIAN BIOCHEMIST Page 3 SHOWCASE ON RESEARCH Haematopoietic Stem Cells Ashley Ng1,2,3* and Warren Alexander1,2 1Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052 2Department of Medical Biology, University of Melbourne, Parkville, VIC 3010 3Department of Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Parkville, VIC 3050 *Corresponding authors: [email protected] Introduction they were eventually identified. Haematopoietic stem cells (HSCs) are the architects of The identification and characterisation of HSCs required definitive haematopoiesis, that is, blood cell production strategies to separate these rare bone marrow cells from that occurs continuously throughout the life of an organism. other more numerous cellular bone marrow components. Each HSC is programmed to allow the efficient production Functional competitive repopulating unit assays estimated of the cellular components of blood with a manifest purpose the frequency of these rare cells in bone marrow as 1 in that has been shaped by evolution. This can be observed 10,000 cells (13). Like the proverbial search for the needle in from red cells that have evolved to allow efficient carriage a haystack, HSCs were eventually isolated with increasing of oxygen, megakaryocytes and their platelet progeny that purity based on physical properties, such as Hoescht 33342 interact with blood vessels and soluble coagulation factors supravital dye exclusion (14), resistance to 5-fluorouracil to regulate clotting, to the cells of the innate and acquired (15) or gamma-irradiation (16). Ultimately, however, it immune systems that act against microbial attack. HSCs was the advent of flow cytometry and the use of specific are defined by their pluripotentiality: the capacity for a surface antigen markers (17) that led to the prospective single HSC to generate any and all of the diverse mature identification of cell populations able to reconstitute functional haematopoietic cell types, with key genes and multiple lineages upon transplantation into primary select genetic programmes invoked for the maintenance or recipients, and capable of self-renewal as judged by serial self-renewal of HSCs and for the formation of the specific transplantation assays. These cell populations
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