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Embryonic Stem Cell Differentiation Laboratory
Group Leaders: Professors: Andrew Elefanty and Ed Stanley
Postal Address
Embryonic Stem Cell Differentiation Laboratory Monash Immunology and Stem Cell Laboratories Level 3, Building 75, STRIP 1, West Ring Road Monash University Clayton, Victoria 3800
Image Gallery
Current laboratory members
Research Fellows
Dr Magdaline Costa
Dr David Elliott
Dr Karin Gertow
Ms Tanya Hatzistavrou
Dr Susan Hawes
Dr Philip Heraud
Dr Claire Hirst
Dr Andrew Holland
Dr Vanta Jokubaitis
Dr Sue Mei Lim
Dr Xueling Li
Dr Suzanne Micallef
Ms Elizabeth Ng
Research Assistants
Ms Lisa Azzola
Ms Amanda Bruce
Ms Aude Conscience
Ms Sonia Holland
Ms Robyn Mayberry
Ms Koula Sourris
Ms Kathy Koutsis
PhD students
Ms Julie Cao
Ms Jennifer Durnall
Mr Adam Goulburn
Mr Rob Jenny
Ms Elizabeth Ng (part time)
Ms Jacqueline Schiesser
Ms Chew-Li Soh
Mr Michael Wong
Ms Cissy Yu
Research Overview
Research in the laboratory that jointly headed by Prof. Andrew Elefanty and Prof. Ed Stanley is focused on the biology and manipulation of human embryonic stem (ES) cells. Our major interest is in the regulation of ES cell differentiation to mesendodermal precursors (corresponding to the primitive streak in the mammalian embryo) and then to mesodermal and endodermal lineages, as exemplified by blood, heart and endothelium and pancreatic islet cells, respectively.
In order to facilitate this process, we are generating genetically modified human ES cell lines into which reporter genes have been inserted by homologous recombination in gene loci that are expressed at specific developmental stages or in specific lineages.
For example, mesendodermal precursors are identified by the expression of a homeobox gene, MIXL1, that we cloned a few years ago. Our laboratory has generated human ES cells that carry GFP reporter genes inserted by homologous recombination into the MIXL1 locus that fluoresce when this gene is transiently expressed during differentiation. These cell lines, and additional lines tagged at other gene loci relevant to blood, heart and pancreatic lineages, are proving to be valuable tools for the dissection of differentiation pathways towards mesoderm and endoderm in vitro.
A major goal of our work is to realise some of the scientific and therapeutic potential that human ES cells promise. These include unique opportunities for the study of early stages of human development, the generation of in vitro models for human diseases, testing of pharmaceuticals and other therapeutic products and the production of transplantable cells for tissue repair and regeneration.
Publications 2005 – 2009
Micallef SJ, Janes ME, Knezevic K, Davis RP, Elefanty AG and Stanley EG. Retinoic acid induces Pdx1-positive endoderm in differentiating mouse embryonic stem cells. Diabetes, 54, 301-5, 2005.
Ng ES, Azzola L, Sourris K, Robb L, Stanley EG, Elefanty AG. The primitive streak gene, Mixl1, is required for efficient haematopoiesis and BMP4-induced ventral mesoderm patterning in differentiating ES cells. Development, 132, 873-884, 2005.
Costa M, Dottori M, Ng ES, Hawes SM, Sourris K, Jamshidi P, Pera MF, Elefanty AG and Stanley EG. The hESC line Envy expresses high levels of GFP in all differentiated progeny. Nat Methods, 2, 259-260, 2005.
D'Souza SL, Elefanty AG and Keller G. SCL/Tal-1 is essential for hematopoietic commitment of the hemangioblast but not for its development. Blood, 105, 3862-70, 2005.
Ng ES, Davis RP, Azzola L, Stanley EG and Elefanty AG. Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation. Blood, 106, 1601-3, 2005.
Mossman AK, Sourris K, Ng E, Stanley EG and Elefanty AG. Mixl1 and Oct4 proteins are transiently co-expressed in differentiating mouse and human embryonic stem cells. Stem Cells Dev, 14, 656-663, 2005.
Hirst CE, Ng ES, Azzola L, Voss AK, Thomas T, Stanley EG and Elefanty AG. Transcriptional profiling of mouse and human ES cells identifies SLAIN1, a novel stem cell gene. Dev Biol, 293, 90-103, 2006.
Holland AM, Micallef SJ, Li X, Elefanty AG and Stanley EG. A mouse carrying the green fluorescent protein gene targeted to the pdx1 locus facilitates the study of pancreas development and function. Genesis, 44, 304-307, 2006.
Costa M, Dottori M, Sourris K, Jamshidi P, Hatzistavrou T, Davis R, Azzola L, Jackson S, Lim SM, Pera M, Elefanty AG and Stanley EG. A method for genetic modification of human embryonic stem cells using electroporation. Nature Protocols, 2, 792-796, 2007.
Pick M, Azzola L, Mossman A, Stanley EG and Elefanty AG. Differentiation of human embryonic stem cells in serum free medium reveals distinct roles for BMP4, VEGF, SCF and FGF2 in hematopoiesis. Stem Cells, 25, 2206-2014, 2007
Micallef SJ, Li X, Janes ME, Jackson SA, Sutherland RM, Lew AM, Harrison LC, Elefanty AG and Stanley EG. Endocrine cells develop within pancreatic bud-like structures derived from mouse ES cells differentiated in response to BMP4 and retinoic acid. Stem Cell Research, 1, 25-36, 2007
Costa M, Sourris K, Hatzistavrou T, Elefanty AG and Stanley EG. Expansion of human embryonic stem cells in vitro. Curr Protoc Stem Cell Biol, 1:1C.1.1 - 1C.1.7, 2007.
Micallef SJ, Li X, Elefanty AG and Stanley EG. Pancreas differentiation of mouse ES cells Curr Protoc Stem Cell Biol, 2:1G.2.1- 1G.2.8, 2007.
Coultas L, Terzano S, Thomas T, Voss A, Reid K, Stanley EG, Scott CL, Bouillet P, Bartlett P, Ham J, Adams JM, Strasser A. Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis. J Cell Sci. 120, 2044-52, 2007.
Elefanty AG. Inaugural issue of Stem Cell Research. Stem Cell Res, 1, 1-2, 2007.
Smith J, Wardle F, Loose M, Stanley E, and Roger Patient. Germ Layer Induction in ESC-Following the Vertebrate Roadmap (Review). Curr Protoc Stem Cell Biol, 1:1D.1.1 - 1D.1.22, 2007
Trounson A and Elefanty A. Stem cells in biology, tissue engineering and medicine: the leading edge keeps moving. Curr Opin Biotechnol, 18, 432-3, 2007.
Davis RP, Ng ES, Costa M, Mossman AK, Sourris K, Elefanty AG and Stanley EG. Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors. Blood, 111, 1876-1884, 2008
Ng ES, Davis RP, Hatzistavrou T, Stanley EG and Elefanty AG. Directed differentiation of human embryonic stem cells as spin embryoid bodies and a description of the hematopoietic blast colony forming assay. Curr Protoc Stem Cell Biol, 4:1D.3.1-1D.3.23, 2008
Ng ES, Davis R, Stanley EG and Elefanty AG. A protocol describing the use of a recombinant protein-based, animal product free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies. Nature Protocols, 3, 768-776, 2008.
Stanley EG and Elefanty AG. Building better beta cells. Cell Stem Cell, 2, 300-301, 2008.
Davis RP, Costa M, Grandela C, Holland AM, Hatzistavrou T, Micallef SJ, Li X, Goulburn AL, Azzola L, Elefanty AG and Stanley EG. A protocol for removal of antibiotic resistance cassettes from human embryonic stem cells genetically modified by homologous recombination or transgenesis. Nature Protocols, 3, 1550-1558, 2008.
Lim SM, Pereira L, Wong MS, Hirst CE, Van Vranken BE, Pick M, Trounson A, Elefanty AG and Stanley EG. Enforced expression of Mixl1 during mouse ES cell differentiation suppresses hematopoietic mesoderm and promotes endoderm formation. Stem Cells, 27, 363-374, 2009.
Holland AM, Elefanty AG and Stanley EG. Pancreatic differentiation from pluripotent stem cells: tweaking the system. Cell Research 19:395-6, 2009.
Hatzistavrou T, Micallef SJ, Ng ES, Vadolas J, Stanley EG and Elefanty AG. ErythRED, a hESC line enabling easy identification of erythroid cells, Nature Methods 6, 659 - 662, 2009.
Davis RP, Grandela C, Dottori M, Hatzistavrou T, Sourris K, Elefanty AG, Stanley EG and Costa M. Generation of human embryonic stem cell reporter knock-in lines by homologous recombination. Curr Protoc Stem Cell Biol, 2009. In press.
Elefanty AG and Stanley EG. Reshaping pluripotent stem cells. Nature Biotechnology 27, 823-824, 2009.
Research Support
National Health and Medical Research Council of Australia
Australian Stem Cell Centre (an ARC centre of Excellence)
Juvenile Diabetes Research Foundation
The National Heart Foundation of Australia
The Victoria-California Stem Cell Alliance
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