Module 3: Characterisation of Pancreatic, Respiratory & Thymic Epithelium Derived from the In Vitro Differentiation of Pluripotent Stem Cells

 Module Leaders Professor Ed Stanley
Host Organisation
 Monash Immunology and Stem Cell Laboratories (MISCL), Monash University

Module description

The endoderm program encompasses research focused on the generation and characterisation of thymic and respiratory cells derived from the in vitro differentiation of pluripotent stem cells. These two cell types share overlapping developmental pathways that involve conceptually related mechanisms of specification, patterning and tissue elaboration.

This Module’s strategy is to guide hESC differentiation along the same developmental pathways transited by cells within the embryo, recapitulating aspects of the ontogeny of tissue formation in vitro. To help monitor this process, the laboratory have generated a number of genetically tagged hESC lines in which a reporter gene has been inserted into key loci that mark critical milestones in the development of each cell type.

Hypotheses

Thymic and respiratory epithelial cells generated from the in vitro differentiation of human embryonic stem cells will provide a valuable platform for future medical research into the biology of these two cell types.

Module Leader biography

Professor Ed Stanley was trained in the area of colony stimulating factors under the supervision of Dr. Ashley Dunn at the Ludwig Institute for Cancer Research. Following completion of his Ph.D., Professor Stanley was awarded a Human Frontiers in Science Organisation Fellowship prior to taking up a CJ. Martin Fellowship. These fellowships allowed him to relocate to the National Institute for Medical Research, Mill Hill, London, where he studied HOX gene regulation, before returning to the Walter and Eliza Hall Institute of Medical Research (WEHI). In 2000, he was appointed Head of the Embryonic Stem Cell laboratory at WEHI before moving, at the beginning of 2002, to the Centre for Early Human Development at the Monash Institute for Reproduction and Development.

Contact details

Professor Ed Stanley
 E-mail  ed.stanley@med.monash.edu.au
 Phone   +61 3 9905-0651
 Web  www.med.monash.edu.au/miscl

Selected publications

  1. 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. (IF=14.9)
  2. 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. (IF=10.1)
  3. 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. (IF=1.5)
  4. Wong SHA, Lowes KN, Bertoncello I, Cook MJ, Simmons PJ, Kornberg AJ, Kapsa RMI. (2007) Evaluation of Sca-1 and c-Kit as selective markers for muscle remodelling by non-hemopoietic bone marrow cells. Stem Cells 25:1364-1374. (IF = 7.531)
  5. 16. Jokubaitis VJ, Sinka L, Driessen R, Whitty G, Haylock DN, Bertoncello I, Smith I, Péault B, Tavian M, Simmons PJ. (2008) Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, adult hematopoietic tissues. Blood 111:4055-4063.(IF = 10.8)
  6. 17. Williams BB, Wall M, Miao RY, Williams B, Bertoncello I, Kershaw MH, Mantamadiotis T, Haber M, Norris MD, Gautam A, Darcy PK, Ramsay RG. (2008) Induction of T cell-mediated immunity using a c-Myb DNA vaccine in a mouse model of colon cancer. Cancer Immunol Immunother 57:1635-1645 (IF = 3.728)
  7. McQualter JL, Brouard N, Williams B, Baird BN, Sims-Lucas S, Yuen K, Nilsson SK, Simmons PJ, Bertoncello I. (2009) Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in he Sca-1 positive cell fraction (2009). Stem Cells 3:623-3
  8. Chidgey AP, Layton DS, Trounson AO, Boyd,RL. (2008) Tolerance strategies for stem-cell-based therapies. Nature, 453, 330 – 337. IF: 28.751
  9. Kelly RM, Highfill SL, Panoskaltsis-Mortari A, Taylor PA, Boyd RL, Hollander GA, and Blazar BR (2008) Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution following murine bone marrow transplantation. Blood 111(12): 5734-44. (IF: 10.8)
  10. Barnard AL, Chidgey AP, Bernard CA, Boyd RL. (2008) Androgen depletion increases the efficacy ofbone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis. Blood 113: 204 -213. (IF: 10.8)
  11. Chidgey AP, Boyd RL., (2008) Immune privilege for stem cells: not as simple as it looked. Cell Stem Cell 3(4): 357 – 358