Module 4: Transcriptomic and Epigenomic Analysis of Pluripotency and iPS Utility

Module Leader Professor Sean Grimmond
Host Organisation Institute of Molecular Bioscience, University of Queensland

Module description

Major goals of this module are defining the underlying genetics controlling deprogramming, maintenance of pluripotency and directed differentiation of cell types from iPS lines of specific genotypes. The laboratory have recently piloted an investigation of genome wide gene expression and methylation signatures of hES lines, iPS subclone lines and their parent cell lines with the support of the Queensland Government. The work is currently being undertaken in the Thomson iPS lines. This is being undertaken to assess what key epigenomic signatures are changed as a consequence of reprogramming as well as defining the gene activity required to maintain pluripotency.

Once this foundation dataset is completed in the short term, the key aims of this module will be to assess the transcriptomic and epigenomic signatures of iPS cell lines made with different methods from both within the ASCC and other laboratories.

This data will provide valuable insights in to the scale and heterogeneity in the epigenomic signatures left after reprogramming and will give researchers a yard stick to measure to the quality of reprogramming obtained.

Aims

  1. Developing a better understanding of the underlying molecular events required to drive reprogramming.
  2. Creation of foundation data for the modeling of the genetic-epigenetic networks of pluripotency.
  3. The identification of epigenetic signatures that influence lineage differentiation.
  4. Development of genomic screening tools to assess iPS line quality.

    Module Leader biography

    Professor Sean Grimmond is an NHMRC Senior Research Fellow who established the IMB's Expression Genomics laboratory in 2001. His work is centred at the intersection of bioinformatics, genomics and cell biology and its underlying theme is the accurate characterisation of the transcriptome and the identification of transcriptional programs or gene networks controlling cellular phenotypes in human development and disease.

    These studies involve an integrated pipeline approach to large scale transcriptome annotation, genome wide surveys of gene expression, computational prediction of gene function and transcriptional programs, and the validation of lead genes function. This pipeline approach has been successfully used to screen the mammalian genome/transcriptome/proteome f or key secreted factors/cell surface markers of ES cell, haematopoietic differentiation, organogenesis and renal repair and is now being extended to study ES cell differentiation, cell division and tumorigenesis.

    Contact details

     E-mail  s.grimmond@imb.uq.edu.au  
     Phone  +61 7 3346 2057
     Web
    		 www.imb.uq.edu.au/?page=11662

    Selected publications

    1. Grimmond S, Lagercrantz J, Drinkwater C, Silins G, Townson S, Pollock P, Gotley D, Carson E, Rakar S, Nordenskjöld M, Ward L, Hayward N, Weber G (1996) Cloning and characterization of a novel human gene related to vascular endothelial growth factor. Genome Research, 2, 21-29.  IF: 10.14    Citations: 81
    2. The FANTOM Consortium and The RIKEN Genome Exploration Research Group Phase I & II Team (Grimmond SM) (2002) Analysis of the Mouse Transcriptome based upon Functional Annotation of 60,770 full length cDNAs. Nature, 420 (6915), 563-73.  IF: 29.17  Citations: 491
    3. Ravasi T, Huber T, Zavolan M, Forrest A, Gaasterland T, Grimmond S, RIKEN GER Group Members Hume DA (2003) Systematic characterization of the zinc finger containing proteins in the mouse transcriptome. Genome Research, 13, 1430-42.  IF: 10.14  Citations: 25
    4. Forrest A, Ravasi T, Hume D, Taylor D, Huber T, RIKEN GER Group Members, Grimmond SM (2003) Protein Phosphoregulators: Protein Kinases and protein phosphatases of the mouse. Genome Research, 13, 1443-54.IF: 10.14   Citations: 18
    5. Kanapin A, Gough J, Grimmond SM, Davis M, RIKEN GER Group Members, Teasdale RD (2003) The mammalian proteome. Genome Research, 13, 1335-44. IF: 10.14  Citations: 19
    6. Gustincich S, Arakawa Y, Batalov S, Beisel KW, Bono H, Carninci P, Fletcher CF, Grimmond SM, Hirokawa N, Jarvis ED, Jegla T, Kawasaka Y, Miki H, Raviola E, Teasdale RD, Waki K, Zimmer A, Kawai J, Hayashizaki Y, Okazaki Y (2003) Analysis of the mouse transcriptome for genes involved in the function of the nervous system. Genome Research, 13, 1395-01.  IF: 10.14  Citations: 6
    7. Forrest A, Taylor, D, RIKEN GER Group Members, Grimmond S (2003) Cell cycle regulators of the mouse. Genome Research, 13, 1366-75.  IF: 10.14   Citations: 5
    8. Grimmond S, Miranda K, Yuan Z, RIKEN GER Group Members, Teasdale RD (2003) The Mouse Secretome: Functional Classification of the Proteins Secreted Into the Extracellular Environment. Genome Research, 13, 1350-59.IF: 10.14  Citations: 29
    9. de Sousa Nunes R, Rana A, Kettleborough R, Brickman J, Clements M, Rodriguez TA,Forrest A, Bullock S, Martinez Barbera JP, Grimmond SM, Avner P, Smith JC, Dunwoodie SL, Beddington RSP (2003) Characterising Embryonic Gene Expression Using a Non-Redundant Sequence-Based Selection Method. Genome Research, 13, 2609-20.IF: 10.14   Citations: 11
    10. Srikhanta YN, Maguire TL, Stacey KJ, Grimmond SM, Jennings MP (2005) The Phasevarion: a novel system controlling coordinated, random switching of expression of multiple genes. Proc Natl Acad Sci U S A, 102 (15), 5547-51.  IF: 10.31   Citations: 12