Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis Robert J. Chen, MD,...
Backgrounds: Heart Failure <ul><li>End-stage heart failure </li></ul><ul><ul><li>Current: Heart transplantation </li></ul>...
Background: Stem Cells <ul><li>Embryonic stem cells: ethics? </li></ul><ul><li>Adult stem cells </li></ul><ul><ul><li>Exis...
 
 
 
 
 
 
 
 
Objective <ul><li>Induced pluripotent stem (iPS) cells </li></ul><ul><ul><li>SOX2 -OCT4-NANOG complex (ectopically induced...
Methods <ul><li>NCBI online Entrez Gene and Pubmed </li></ul><ul><li>Literature review </li></ul><ul><li>To identify candi...
Methods <ul><li>Ingenuity Pathway Analysis (IPA) 7.5 ® </li></ul><ul><li>Pathway network of the interactants with GNL3 and...
 
 
 
Functional Network <ul><li>Molecules related to cardiovascular system development and function: </li></ul><ul><ul><li>CDKN...
Canonical Pathways <ul><li>PPP2R5A: cardiac beta-adrenergic signaling </li></ul><ul><li>Fgf (fibroblast growth factor): hu...
Conclusion <ul><li>In the exploratory analysis, the functional pathway networks of nucleostemin and iPS interact via: </li...
 
 
 
 
 
Thank you! ( Rjcc@ntu.edu.tw)
 
 
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Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis

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In the exploratory analysis, the functional pathway networks of nucleostemin and iPS interact via TP53 (tumor protein P53) and Fgf (fibroblast growth factor), which could be further investigated to provide clues for the future research of postnatal cardiac regeneration.

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Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis

  1. 1. Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis Robert J. Chen, MD, MPH ( [email_address] ) *Yau-Hua Yu, DDS, DMsc Dept. of Cardiac Surg., Cheng-Hsin Hosp. Heart Center; Graduate Inst. of Epidemiology, Nat’l Taiwan Univ. *School of Dentistry, Nat’l Yang-Ming Univ.; *Dept. of Dentistry and Dept. of Med. Research and Education, Taipei Veterans General Hosp., Taipei, Taiwan
  2. 2. Backgrounds: Heart Failure <ul><li>End-stage heart failure </li></ul><ul><ul><li>Current: Heart transplantation </li></ul></ul><ul><ul><li>Pitfalls: donor, infection, rejection, … </li></ul></ul><ul><ul><li>Alternatives: IABP, ECMO, VAD,… </li></ul></ul><ul><li>Future </li></ul><ul><ul><li>Xeno-transplantation? </li></ul></ul><ul><ul><li>Stem cells and regeneration! </li></ul></ul>
  3. 3. Background: Stem Cells <ul><li>Embryonic stem cells: ethics? </li></ul><ul><li>Adult stem cells </li></ul><ul><ul><li>Existing stem cells: harvesting? </li></ul></ul><ul><ul><li>Induced pluripotent stem (iPS) cells </li></ul></ul><ul><ul><ul><li>Reprogrammed from somatic cells </li></ul></ul></ul><ul><ul><ul><li>Re-differentiate and regenerate into a new heart </li></ul></ul></ul>
  4. 12. Objective <ul><li>Induced pluripotent stem (iPS) cells </li></ul><ul><ul><li>SOX2 -OCT4-NANOG complex (ectopically induced transcription factors) </li></ul></ul><ul><ul><li>RepSox + OCT4-NANOG (Harvard, 2009) </li></ul></ul><ul><li>Nucleostemin (GNL3) </li></ul><ul><ul><li>Pivotal role in cardiac repair </li></ul></ul><ul><li>Interplay of GNL3 in iPS cells? </li></ul><ul><li>Bioinformatics exploration </li></ul>
  5. 13. Methods <ul><li>NCBI online Entrez Gene and Pubmed </li></ul><ul><li>Literature review </li></ul><ul><li>To identify candidates molecules that interact with the following molecules. </li></ul><ul><ul><li>Nucleostemin (GNL3) </li></ul></ul><ul><ul><li>SOX2 </li></ul></ul><ul><ul><li>OCT4 (POU5F1) </li></ul></ul><ul><ul><li>NANOG </li></ul></ul>
  6. 14. Methods <ul><li>Ingenuity Pathway Analysis (IPA) 7.5 ® </li></ul><ul><li>Pathway network of the interactants with GNL3 and SOX2-OCT4-NANOG </li></ul><ul><li>Functional analysis </li></ul><ul><ul><li>Patho-physiological processes </li></ul></ul><ul><ul><li>Canonical pathways </li></ul></ul>
  7. 18. Functional Network <ul><li>Molecules related to cardiovascular system development and function: </li></ul><ul><ul><li>CDKN2A </li></ul></ul><ul><ul><li>TP53 (tumor protein p53) </li></ul></ul><ul><ul><li>ID3 </li></ul></ul><ul><ul><li>NPM1 </li></ul></ul><ul><ul><li>IL2 </li></ul></ul><ul><li>P-value=8.4e-4 ~ 9.9e-4 by right-tailed Fisher Exact Test </li></ul>
  8. 19. Canonical Pathways <ul><li>PPP2R5A: cardiac beta-adrenergic signaling </li></ul><ul><li>Fgf (fibroblast growth factor): human embryonic stem cell pluripotency. </li></ul><ul><li>Nucleostemin (GNL3) interacts with NANOG of the iPS network via two molecules </li></ul><ul><ul><li>Fgf </li></ul></ul><ul><ul><li>TP53. </li></ul></ul>
  9. 20. Conclusion <ul><li>In the exploratory analysis, the functional pathway networks of nucleostemin and iPS interact via: </li></ul><ul><ul><li>TP53 (tumor protein P53) </li></ul></ul><ul><ul><li>Fgf (fibroblast growth factor) </li></ul></ul><ul><li>They could be further investigated to provide clues for the future research of postnatal cardiac regeneration. </li></ul>
  10. 26. Thank you! ( Rjcc@ntu.edu.tw)

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