induced pluripotent stem cells and somatic cardiac regeneration— an exploratory bioinformatic...

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Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis Robert J. Chen, MD, MPH ( [email protected] ) *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.

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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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Page 1: Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis

Induced Pluripotent Stem Cells and Somatic Cardiac

Regeneration— An Exploratory Bioinformatic Analysis

Induced Pluripotent Stem Cells and Somatic Cardiac

Regeneration— An Exploratory Bioinformatic Analysis

Robert J. Chen, MD, MPH ([email protected])

*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

Robert J. Chen, MD, MPH ([email protected])

*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

Page 2: Induced Pluripotent Stem Cells and Somatic Cardiac Regeneration— An Exploratory Bioinformatic Analysis

Backgrounds: Heart FailureBackgrounds: Heart Failure

End-stage heart failure Current: Heart transplantation Pitfalls: donor, infection, rejection, … Alternatives: IABP, ECMO, VAD,…

Future Xeno-transplantation? Stem cells and regeneration!

End-stage heart failure Current: Heart transplantation Pitfalls: donor, infection, rejection, … Alternatives: IABP, ECMO, VAD,…

Future Xeno-transplantation? Stem cells and regeneration!

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Background: Stem CellsBackground: Stem Cells

Embryonic stem cells: ethics? Adult stem cells

Existing stem cells: harvesting? Induced pluripotent stem (iPS) cells

Reprogrammed from somatic cells Re-differentiate and regenerate into a new heart

Embryonic stem cells: ethics? Adult stem cells

Existing stem cells: harvesting? Induced pluripotent stem (iPS) cells

Reprogrammed from somatic cells Re-differentiate and regenerate into a new heart

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ObjectiveObjective

Induced pluripotent stem (iPS) cells SOX2-OCT4-NANOG complex (ectopically induced

transcription factors) RepSox + OCT4-NANOG (Harvard, 2009)

Nucleostemin (GNL3) Pivotal role in cardiac repair

Interplay of GNL3 in iPS cells? Bioinformatics exploration

Induced pluripotent stem (iPS) cells SOX2-OCT4-NANOG complex (ectopically induced

transcription factors) RepSox + OCT4-NANOG (Harvard, 2009)

Nucleostemin (GNL3) Pivotal role in cardiac repair

Interplay of GNL3 in iPS cells? Bioinformatics exploration

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MethodsMethods NCBI online Entrez Gene and Pubmed Literature review To identify candidates molecules that

interact with the following molecules. Nucleostemin (GNL3) SOX2 OCT4 (POU5F1) NANOG

NCBI online Entrez Gene and Pubmed Literature review To identify candidates molecules that

interact with the following molecules. Nucleostemin (GNL3) SOX2 OCT4 (POU5F1) NANOG

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MethodsMethods

Ingenuity Pathway Analysis (IPA) 7.5 ® Pathway network of the interactants with

GNL3 and SOX2-OCT4-NANOG Functional analysis

Patho-physiological processes Canonical pathways

Ingenuity Pathway Analysis (IPA) 7.5 ® Pathway network of the interactants with

GNL3 and SOX2-OCT4-NANOG Functional analysis

Patho-physiological processes Canonical pathways

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Functional NetworkFunctional Network

Molecules related to cardiovascular system development and function: CDKN2A TP53 (tumor protein p53) ID3 NPM1 IL2

P-value=8.4e-4 ~ 9.9e-4 by right-tailed Fisher Exact Test

Molecules related to cardiovascular system development and function: CDKN2A TP53 (tumor protein p53) ID3 NPM1 IL2

P-value=8.4e-4 ~ 9.9e-4 by right-tailed Fisher Exact Test

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Canonical PathwaysCanonical Pathways

PPP2R5A: cardiac beta-adrenergic signaling Fgf (fibroblast growth factor): human embryonic

stem cell pluripotency. Nucleostemin (GNL3) interacts with NANOG of

the iPS network via two molecules Fgf TP53.

PPP2R5A: cardiac beta-adrenergic signaling Fgf (fibroblast growth factor): human embryonic

stem cell pluripotency. Nucleostemin (GNL3) interacts with NANOG of

the iPS network via two molecules Fgf TP53.

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ConclusionConclusion

In the exploratory analysis, the functional pathway networks of nucleostemin and iPS interact via: TP53 (tumor protein P53) Fgf (fibroblast growth factor)

They could be further investigated to provide clues for the future research of postnatal cardiac regeneration.

In the exploratory analysis, the functional pathway networks of nucleostemin and iPS interact via: TP53 (tumor protein P53) Fgf (fibroblast growth factor)

They could be further investigated to provide clues for the future research of postnatal cardiac regeneration.

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Thank you!([email protected])

Thank you!([email protected])

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