iPS Cell Regeneration and Cardiac Stem Cells
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This document summarizes an exploratory bioinformatic analysis of the interplay between induced pluripotent stem cells and somatic cardiac regeneration. The analysis identified molecules like nucleostemin that interact with key transcription factors involved in inducing pluripotency. Pathway analysis revealed networks linking nucleostemin and these factors to processes involved in cardiovascular development and the maintenance of pluripotency. Specifically, nucleostemin was found to interact with NANOG, a critical pluripotency factor, via the molecules TP53 and FGF. These findings provide potential targets for further research on using iPS cells to enable postnatal cardiac regeneration.
![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](https://image.slidesharecdn.com/nsips-111128180124-phpapp01/85/Induced-Pluripotent-Stem-Cells-and-Somatic-Cardiac-Regeneration-An-Exploratory-Bioinformatic-Analysis-1-320.jpg)
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iPS Cell Regeneration and Cardiac Stem Cells
- 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
- 26. Thank you! ( Rjcc@ntu.edu.tw)
Hinweis der Redaktion
- Opening
- We need a better therapy for heart failure.
- Stem cell is a good solution, especially iPS.
- iPS is not science fiction. There are some progress. In 2008, mouse iPS was produced into heart cells, published in Circulation.
- Another report of success for iPS into heart cells in mice in 2008. Published also in Circulation.
- In 2008, published in Proceeding of National Academy of Sciences, human iPS was produced. Of note, iPS needs some transcription factors, one of them is c_myc, a pro-oncogene which may not be safe for iPS.
- In 2009, published in Circulation research, human iPS was produced and transformed into functioning heart cells.
- Also in Circulation Research, in 2008, there was a paper talking about nucleostemin. It enhances cardiac repair and maybe regeneration.
- The editorial in the same issue of Circulation Research discussed the possible role of nucleostemin in cardiac stem cells.
- Here is the proposed mechanism of nucleostemin in cardiac regeneration, via a network of molecules.
- Nucleostemin and iPS networks may have interactions? Before lab, we would like a “dry lab” exploration by bioinformatics tools.
- We used online tools and look up possible molecules.
- We also used the commercial software to construct the pathways and networks, including the function analysis of patho-physiological processes and canonical pathways.
- It’s the iPS network. POU5F1 is OCT4. Both of SOX2 and OCT4 function inside the nucleus. NANOG interact with SOX2 and OCT4 in an unknown subcellular location.
- It’s the nucleostemin (GNL3) network, involving more molecules, in different subcellular compartments. Some molecules already relate to cardiac function.
- When we combined the two networks, we found they interact via NANOG in the intra-nuclear location. The interacting molecules are Fgf and TP53.
- In the previous functional network, we found the following molecules have cardiac-related functions: CDKN2A, TP53, ID3, NPM1, and IL2.
- When we look at the canonical pathways, we found PPP2R5A relates to beta-adrenergic signaling and Fgf involves in human embryonic stem cells pluripotency. To our interest, the two networks are connected via NANOG with two common molecules: Fgf and TP53.
- Nucleostemin (GNL3) may involve in iPS with NANOG and two other molecules: TP53 and Fgf. Molecular biologists may proceed “wet lab” to further investigate the interactions.
- This year, Harvard’s team found a molecule, RepSox, could make iPS and eliminate one transcription factor SOX2. In the future, iPS ma be produced in cell-free condition, just needing some molecules like drugs. Try to imagine, if we need a new heart, just take a skin biopsy and immerse the cells into a special solution. It turnd into iPS and then grow into a new heart from our own cells.
- Harvard team’s RepSox inhibits Tgf-beta signaling to make iPS.
- This is a blueprint of cardiac regeneration from iPS.
- This picture was taken in Cesky Krumlov, Czech Republic two weeks ago. There are lots of houses but only few have treasure and gold. We must find a good method to locate them. Our study is just a beginning to the long but promising journey of cardiac regeneration.
- Thank you very much.