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Human Embryonic Stem Cell Technology
Group Leader
Andrew Laslett, PhD
Senior Scientist
Contact Details
Email: andrew.laslett@stemcellcentre.edu.au
To find out more about Andrew Laslett, PhD, click here.
Lab Members
Hun Chy - Research Assistant
Mirabelle Ho – PhD Student
Christina Jones - PhD Student (co-supervised with Sharon Ricardo, MISCL, Monash University)
Jordan Kane - PhD Student (co-supervised with Christina Mitchell, Biochemistry, Monash University)
Adelia Lin - PhD Student
George Qi Zhou - Research Scientist, Embryonic Stem Cells
Research Focus
Our research examines the basic biology of human embryonic stem cells (hESC).
Initially we have focussed on phenotypic characterisation of subpopulations within human ES cell colonies and more recently have begun examining the differentiation of hESC to a renal fate.
Overview
(i) Refining the human embryonic stem cell phenotype
Thus far, our research, has demonstrated that we can isolate viable pluripotent (Oct-4+) human ES cells from a heterogenous mixture of cells by selecting for two surface markers. This is important as this methodology provides a facile means for the separation of Oct-4+ cells from Oct-4– human ES cells without insertion of selectable markers. We have transcriptionally profiled subpopulations of hESC delineated using these cell surface markers. Current projects focus on gaining a better understanding of both the maintenance of the stem cell state and the decisions hESC make when becoming committed to a specific lineage.
(ii) Induction and identification of renal cells from differentiating hESC
Chronic renal failure is a debilitating problem affecting large numbers of people. The only current treatment options are dialysis and renal transplantation. Dialysis is expensive, time consuming and has a high (~16%) mortality rate. Transplantation is preferable, but a worldwide shortage in available organs means only 1 in 4 patients awaiting a kidney transplant will receive one. Therefore, technology enabling the production of functional renal cells to be used in transplantation, or as an adjunct to dialysis in conjunction with a bioartificial kidney, is widely awaited. This project examines methods to direct the differentiation of hESC cells to primitive renal cells and to develop models to test their ability to incorporate into developing, damaged and diseased kidneys (in collaboration with Dr Sharon Ricardo, MISCL).
Funding
Kidney Health Australia
NHMRC
Selected Publications
Gubhaju L, Laslett AL, Bertram JF, Zulli A, Black JM. Immunohistochemical localisation of TRA-1-60, GCTM-2 and podocalyxin in the developing baboon kidney. Histochem Cell Biol 2008 (in press)
Filipczyk AA, Laslett AL, Mummery C & Pera MF. Differentiation is coupled to changes in the cell cycle regulatory apparatus of human embryonic stem cells. Stem Cell Research 2007;1:1; 45-60.
Laslett AL, Grimmond S, Gardiner B, Stamp L, Lin A, Hawes SM, et al. Transcriptional Analysis of Early Lineage Commitment In Human Embryonic Stem Cells. BMC Dev Biol 2007; Mar 2;7(1):12
Herszfeld D, Wolvetang E, Langton-Bunker E, Chung T-L, Filipczyk AA, Houssami S, et al. CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotechnol. 2006 Mar; 24(3):351-7.
Wu J, Jester WF Jr, Laslett AL, Meinhardt A, Orth JM. Expression of a novel factor, short-type PB-cadherin, in Sertoli cells and spermatogenic stem cells of the neonatal rat testis. J Endocrinol. 2003; 176(3):381-91.
Li LH, Jester WF, Laslett AL, Orth JM. A single dose of Di-(2-ethylhexyl) phthalate in neonatal rats alters gonocytes, reduces sertoli cell proliferation, and decreases cyclin D2 expression. Toxicol Appl Pharmacol. 2000; 166(3):222-29.
Laslett AL, Li LH, Jester Jr. WF, Orth JM. Thyroid hormone downregulates neural cell adhesion molecule expression and affects attachment of gonocytes in Sertoli cell-gonocyte cocultures. Endocrinology. 2000; 141:1633-41.
Laslett AL, McFarlane J, Risbridger GP. Developmental response by Leydig cells to acidic and basic fibroblast growth factor. J Steroid Biochem Mol Biol. 1997; 60(3-4): 171-79.
McFarlane J, Laslett AL, de Kretser DM, Risbridger GP. Evidence that heparin binding autocrine factors modulate testosterone production by the adult rat Leydig cell. Mol Cell Endocrinol. 1996; 118:57-63.
Drummond AE, McPherson SJ, Laslett AL, Hearn MTW. Characterisation of the effect of steroid hormones on the bFGF-mediated stimulation of endothelial cells with a chromogenic cell proliferation bioassay. J Biochem Biophys Methods. 1996; 31:123-34.
Laslett AL, McFarlane J, Hearn MTW, Risbridger GP. Requirement for heparan sulphate proteoglycans to mediate basic fibroblast growth factor (FGF-2) induced stimulation of Leydig cell steroidogenesis. J Steroid Biochem Mol Biol. 1995; 54(5):245-50.
Invited Reviews & Chapters
Laslett AL, Fryga A & Pera MF. Flow cytometric analysis of human embryonic stem cells. In: Loring JF, editor. Human Stem Cell Manual: A Laboratory Guide. Elsevier; 2007. p. 96-107.
Laslett AL, Lin A, Pera MF. Characterization and differentiation of human embryonic stem cells. In: Masters JR, et al, editors. Embryonic Stem Cells. Springer; 2007. p. 27–40.
Pera MF, Laslett AL, Hawes SM, Tellis I, Koh K, Nguyen L. Isolation and characterization of human embryonic stem cells. In: Notarianni E, Evans MJ, editors. Embryonic stem cells: a practical approach. Oxford: University Press; 2006. p. 238-59.
Pera MF, Filipczyk A, Hawes SM, Laslett AL. Isolation, characterization, and differentiation of human embryonic stem cells. Methods Enzymol. 2003; 365: 429-46.
Laslett AL, Filipczyk A & Pera MF. Characterization and culture of human embryonic stem cells. Trends Cardiovasc Med. 2003;13(7):295-301.
Orth JM, Jester Jr. WF, Li LH, Laslett AL. Gonocyte-Sertoli cell interactions during development of the neonatal rodent testis. Curr Top Dev Biol. 2000; 50:103-24.
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