Poster Presentation ASSCR, AGCTS, ISCT ANZ and Friends Joint Scientific Conference 2019

Identification and Expression of Islet-enriched microRNAs (#217)

Vijit Saini 1 2 , Wilson K.M. Wong 1 , Mugdha V. Joglekar 1 , Guozhi Jiang 3 , Sarang N. Satoor 1 , Ryan J. Farr 1 , Cody-Lee Maynard 1 , Grzegorz J. Maciag 4 , David Liuwantara 5 , Subhshri Sahu 1 , Tejaswini Sharangdhar 1 , Yi Vee Chew 5 , Lindy Williams 5 , Andrzej S. Januszewski 1 , Edwin Lim 6 , Benjamin Heng 6 , Julie Hunter 7 , Anja E. Sorensen 4 , Jennifer R. Gamble 7 , Philip J. O'Connell 5 , Gilles Guillemin 6 , Thomas Loudovaris 8 , Thomas W.H. Kay 8 , Helen E. Thomas 8 , David Martin 9 , Ann M. Simpson 2 , Louise T. Dalgaard 4 , Ronald C. Ma 3 , Wayne J. Hawthorne 5 , Anandwardhan A. Hardikar 1 4
  1. Islet Biology & Diabetes Group | NHMRC Clinical Trials Center, University of Sydney, Sydney, NSW, Australia
  2. School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia
  3. Department of Medicine and Therapeutics | Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
  4. Department of Natural and Environmental Science, Roskilde University, Copenhagen, Denmark
  5. Westmead Institute of for Medical Research, University of Sydney, Sydney, NSW, Australia
  6. Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia
  7. Centre for Endothelium, Vascular Biology Program, Centenary Institute, University of Sydney, Sydney, NSW, Australia
  8. Immunology and Diabetes Group, St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia
  9. Upper GI Surgery, Strathfield Hospital, Sydney, NSW, Australia

Several studies have demonstrated that Dicer-null mouse islet beta cells show up to 90% reduction in insulin gene transcription [1,2,3]. Similar mechanisms are believed to exist in human islet beta cells, but no specific micro(mi)RNAs are yet identified (in humans or mice) to explain the observations made using Dicer-null mouse beta cells. We profiled 758 known and validated miRNAs in ~700 different human tissues (including over 220 human islet preparations) and used machine-learning algorithms to identify a signature of 22 miRNAs that are predictive and associated with insulin gene expression. We generated three sources of Doxycycline-regulated cell lines: human islet-derived progenitor cells (hIPCs), pancreatic ductal cells (PANC-1) and liver cells (HUH7) (not shown), to express each of the 22 different miRNAs. We are assessing the expression of 50 different gene transcripts (islet hormones, transcription factors, key ligands/receptors, glucose transporters) and the selected miRNAs. We aim to generate these data characterising the impact of forced expression of key islet-associated miRNAs on the expression of pancreatic gene transcripts, so as to identify a select set of miRNAs that are necessary and essential for insulin gene transcription. The major aim of this study is to understand if regulated overexpression of key islet miRNAs drives the expression of pancreatic islet transcription factors, key islet-associated genes and major islet hormones. Further studies are planned to identify miRNAs that can be used in a stage-specific regulated overexpression protocol to assess if forced insulin-associated miRNA overexpression could kick-start/boot-up endogenous islet-enriched miRNA expression and if it improves the differentiation potential of hIPCs. If successful, in vitro and in vivo functional studies would be needed to assess their potential for cell replacement therapy in diabetes.

  1. (Lynn F et al 2007 Diabetes)
  2. (Kalius M et al 2011 PLos One)
  3. (Melkam-Zehavi T et al 2011 Embo J)
  • Have you presented your abstract at another international meeting?: Yes