Proteomic Analysis of Human Pluripotent Stem Cell-Derived, Fetal, and Adult Ventricular Cardiomyocytes Reveals Pathways Crucial for Cardiac Metabolism and Maturation

Ellen Poon, Wendy Keung, Yimin Liang, Rajkumar Ramalingam, Bin Yan, Shaohong Zhang, Anant Chopra, Jennifer Moore, Anthony Herren, Deborah K. Lieu, Hau San Wong, Zhihui Weng, On Tik Wong, Yun Wah Lam, Gordon F. Tomaselli, Christopher Chen, Kenneth R. Boheler, Ronald A. Li

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background - Differentiation of pluripotent human embryonic stem cells (hESCs) to the cardiac lineage represents a potentially unlimited source of ventricular cardiomyocytes (VCMs), but hESC-VCMs are developmentally immature. Previous attempts to profile hESC-VCMs primarily relied on transcriptomic approaches, but the global proteome has not been examined. Furthermore, most hESC-CM studies focus on pathways important for cardiac differentiation, rather than regulatory mechanisms for CM maturation. We hypothesized that gene products and pathways crucial for maturation can be identified by comparing the proteomes of hESCs, hESC-derived VCMs, human fetal and human adult ventricular and atrial CMs. Methods and Results - Using two-dimensional-differential-in-gel electrophoresis, 121 differentially expressed (>1.5-fold; P<0.05) proteins were detected. The data set implicated a role of the peroxisome proliferator-activated receptor signaling in cardiac maturation. Consistently, WY-14643, a peroxisome proliferator-activated receptor agonist, increased fatty oxidative enzyme level, hyperpolarized mitochondrial membrane potential and induced a more organized morphology. Along this line, treatment with the thyroid hormone triiodothyronine increased the dynamic tension developed in engineered human ventricular cardiac microtissue by 3-fold, signifying their maturation. Conclusions - We conclude that the peroxisome proliferator-activated receptor and thyroid hormone pathways modulate the metabolism and maturation of hESC-VCMs and their engineered tissue constructs. These results may lead to mechanism-based methods for deriving mature chamber-specific CMs.

Original languageEnglish (US)
Pages (from-to)427-436
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume8
Issue number3
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Pluripotent Stem Cells
Cardiac Myocytes
Proteomics
Peroxisome Proliferator-Activated Receptors
Proteome
Thyroid Hormones
Mitochondrial Membrane Potential
Triiodothyronine
Human Embryonic Stem Cells
Electrophoresis
Gels
Enzymes
Genes

Keywords

  • embryonic stem cells
  • metabolism
  • PGC1alpha protein
  • PPARalpha
  • proteomics
  • thyroid-stimulating hormone

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Proteomic Analysis of Human Pluripotent Stem Cell-Derived, Fetal, and Adult Ventricular Cardiomyocytes Reveals Pathways Crucial for Cardiac Metabolism and Maturation. / Poon, Ellen; Keung, Wendy; Liang, Yimin; Ramalingam, Rajkumar; Yan, Bin; Zhang, Shaohong; Chopra, Anant; Moore, Jennifer; Herren, Anthony; Lieu, Deborah K.; Wong, Hau San; Weng, Zhihui; Wong, On Tik; Lam, Yun Wah; Tomaselli, Gordon F.; Chen, Christopher; Boheler, Kenneth R.; Li, Ronald A.

In: Circulation: Cardiovascular Genetics, Vol. 8, No. 3, 01.01.2015, p. 427-436.

Research output: Contribution to journalArticle

Poon, E, Keung, W, Liang, Y, Ramalingam, R, Yan, B, Zhang, S, Chopra, A, Moore, J, Herren, A, Lieu, DK, Wong, HS, Weng, Z, Wong, OT, Lam, YW, Tomaselli, GF, Chen, C, Boheler, KR & Li, RA 2015, 'Proteomic Analysis of Human Pluripotent Stem Cell-Derived, Fetal, and Adult Ventricular Cardiomyocytes Reveals Pathways Crucial for Cardiac Metabolism and Maturation', Circulation: Cardiovascular Genetics, vol. 8, no. 3, pp. 427-436. https://doi.org/10.1161/CIRCGENETICS.114.000918
Poon, Ellen ; Keung, Wendy ; Liang, Yimin ; Ramalingam, Rajkumar ; Yan, Bin ; Zhang, Shaohong ; Chopra, Anant ; Moore, Jennifer ; Herren, Anthony ; Lieu, Deborah K. ; Wong, Hau San ; Weng, Zhihui ; Wong, On Tik ; Lam, Yun Wah ; Tomaselli, Gordon F. ; Chen, Christopher ; Boheler, Kenneth R. ; Li, Ronald A. / Proteomic Analysis of Human Pluripotent Stem Cell-Derived, Fetal, and Adult Ventricular Cardiomyocytes Reveals Pathways Crucial for Cardiac Metabolism and Maturation. In: Circulation: Cardiovascular Genetics. 2015 ; Vol. 8, No. 3. pp. 427-436.
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AU - Ramalingam, Rajkumar

AU - Yan, Bin

AU - Zhang, Shaohong

AU - Chopra, Anant

AU - Moore, Jennifer

AU - Herren, Anthony

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AU - Lam, Yun Wah

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