Home LiteratureArticle Details
PMID: 18941512 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes.

PloS one ·Vol. 3 ·No. 10 ·2008-00-00 ·Pages e3474

Cao F, Wagner RA, Wilson KD, Xie X, Fu JD, Drukker M, Lee A, Li RA, Gambhir SS, Weissman IL, Robbins RC, Wu JC

Abstract

Human embryonic stem cells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies such as this will serve as the foundation for future clinical applications of stem cell therapies.

MeSH Terms
Animals Cell Differentiation Electrocardiography Embryonic Stem Cells/cytology,transplantation Gene Expression Profiling Graft Survival Humans Mice Models, Animal Myocardial Reperfusion Injury/therapy Myocytes, Cardiac/cytology,transplantation Oligonucleotide Array Sequence Analysis Stem Cell Transplantation/methods Transcription, Genetic Transplantation, Heterologous Treatment Outcome
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Cao Feng
Department of Radiology, Stanford University School of Medicine, Stanford, California, United States of America.
Wagner Roger A
Wilson Kitchener D
Xie Xiaoyan
Fu Ji-Dong
Drukker Micha
Lee Andrew
Li Ronald A
Gambhir Sanjiv S
Weissman Irving L
Robbins Robert C
Wu Joseph C
References (45)
45 references, click to expand
  1. Engineering myocardial tissue.
    Circ Res. 2005 Dec 9;97(12):1220-31 PMID: 16339494
  2. Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells.
    Circulation. 2003 Jun 3;107(21):2733-40 PMID: 12742992
  3. Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization.
    Circ Res. 2003 Jul 11;93(1):32-9 PMID: 12791707
  4. Postnatal changes in caldesmon expression and localization in cardiac myocytes.
    J Anat. 2003 Oct;203(4):369-77 PMID: 14620377
  5. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.
    Nature. 2004 Apr 8;428(6983):668-73 PMID: 15034594
  6. The complete primary structure of the human alpha 1 (VIII) chain and assignment of its gene (COL8A1) to chromosome 3.
    Eur J Biochem. 1991 May 8;197(3):615-22 PMID: 2029894
  7. Hesx1, a homeobox gene expressed by murine embryonic stem cells, maps to mouse chromosome 14, bands A3-B.
    Genomics. 1993 Nov;18(2):464-6 PMID: 7904583
  8. Left ventricular remodeling after acute myocardial infarction.
    Annu Rev Med. 1995;46:455-66 PMID: 7598478
  9. Evidence for serum response factor-mediated regulatory networks governing SM22alpha transcription in smooth, skeletal, and cardiac muscle cells.
    Dev Biol. 1997 Jul 15;187(2):311-21 PMID: 9242426
  10. Development of a self-inactivating lentivirus vector.
    J Virol. 1998 Oct;72(10):8150-7 PMID: 9733856
  11. Embryonic stem cell lines derived from human blastocysts.
    Science. 1998 Nov 6;282(5391):1145-7 PMID: 9804556
  12. Assays for noninvasive imaging of reporter gene expression.
    Nucl Med Biol. 1999 Jul;26(5):481-90 PMID: 10473186
  13. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells.
    Nat Med. 2005 Apr;11(4):367-8 PMID: 15812508
  14. The initiation of liver development is dependent on Foxa transcription factors.
    Nature. 2005 Jun 16;435(7044):944-7 PMID: 15959514
  15. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials.
    Circulation. 2005 Aug 30;112(9 Suppl):I150-6 PMID: 16159808
  16. SRC family kinase activity is required for murine embryonic stem cell growth and differentiation.
    Mol Pharmacol. 2005 Nov;68(5):1320-30 PMID: 15985613
  17. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement.
    FASEB J. 2006 Apr;20(6):661-9 PMID: 16581974
  18. Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes.
    Stem Cells. 2006 Aug;24(8):1956-67 PMID: 16675594
  19. Germ cell nuclear factor is a repressor of CRIPTO-1 and CRIPTO-3.
    J Biol Chem. 2006 Nov 3;281(44):33497-504 PMID: 16954206
  20. Lmo7 is an emerin-binding protein that regulates the transcription of emerin and many other muscle-relevant genes.
    Hum Mol Genet. 2006 Dec 1;15(23):3459-72 PMID: 17067998
  21. Nanog and transcriptional networks in embryonic stem cell pluripotency.
    Cell Res. 2007 Jan;17(1):42-9 PMID: 17211451
  22. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.
    Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1643-8 PMID: 17251350
  23. Gene symbol: KCNQ1.
    Hum Genet. 2007 Feb;120(6):912 PMID: 17438609
  24. Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development.
    Dev Biol. 2007 May 1;305(1):120-32 PMID: 17350610
  25. Transcriptional activation by stimulating protein 1 and post-transcriptional repression by muscle-specific microRNAs of IKs-encoding genes and potential implications in regional heterogeneity of their expressions.
    J Cell Physiol. 2007 Aug;212(2):358-67 PMID: 17443681
  26. Common genetic variation in KCNH2 is associated with QT interval duration: the Framingham Heart Study.
    Circulation. 2007 Sep 4;116(10):1128-36 PMID: 17709632
  27. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts.
    Nat Biotechnol. 2007 Sep;25(9):1015-24 PMID: 17721512
  28. Human embryonic stem cell transplantation to repair the infarcted myocardium.
    Heart. 2007 Oct;93(10):1278-84 PMID: 17566061
  29. Molecular consequences of dominant Bethlem myopathy collagen VI mutations.
    Ann Neurol. 2007 Oct;62(4):390-405 PMID: 17886299
  30. Transcription factor networks in embryonic stem cells and testicular cancer and the definition of epigenetics.
    Epigenetics. 2007 Jan-Mar;2(1):37-42 PMID: 17965618
  31. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells.
    Cell. 2003 May 30;113(5):643-55 PMID: 12787505
  32. Developmental pluripotency-associated 4 (DPPA4) localized in active chromatin inhibits mouse embryonic stem cell differentiation into a primitive ectoderm lineage.
    J Biol Chem. 2007 Nov 9;282(45):33034-42 PMID: 17855347
  33. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps.
    N Engl J Med. 2007 Dec 27;357(26):2687-95 PMID: 18160688
  34. Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents.
    Circ Res. 2008 May 9;102(9):1008-10 PMID: 18436793
  35. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population.
    Nature. 2008 May 22;453(7194):524-8 PMID: 18432194
  36. Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells.
    Stem Cells. 2008 Jul;26(7):1831-40 PMID: 18436862
  37. Features of cardiomyocyte proliferation and its potential for cardiac regeneration.
    J Cell Mol Med. 2008 Dec;12(6A):2233-44 PMID: 18662194
  38. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro.
    Nat Biotechnol. 2000 Apr;18(4):399-404 PMID: 10748519
  39. Significance analysis of microarrays applied to the ionizing radiation response.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21 PMID: 11309499
  40. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes.
    J Clin Invest. 2001 Aug;108(3):407-14 PMID: 11489934
  41. Cardiac dysfunction in hypertrophic cardiomyopathy mutant tropomyosin mice is transgene-dependent, hypertrophy-independent, and improved by beta-blockade.
    Circ Res. 2002 Aug 9;91(3):255-62 PMID: 12169652
  42. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells.
    Circ Res. 2002 Sep 20;91(6):501-8 PMID: 12242268
  43. High-resolution electrophysiological assessment of human embryonic stem cell-derived cardiomyocytes: a novel in vitro model for the study of conduction.
    Circ Res. 2002 Oct 18;91(8):659-61 PMID: 12386141
  44. Use of echocardiography for the phenotypic assessment of genetically altered mice.
    Physiol Genomics. 2003 May 13;13(3):227-39 PMID: 12746467
  45. Genome-wide expression dynamics during mouse embryonic development reveal similarities to Drosophila development.
    Dev Biol. 2005 Dec 15;288(2):595-611 PMID: 16310180
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0003474
Published
2008-00-00
Epub
2008-00-22
Pages
e3474
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2565131
Subset
IM
Grants
NHLBI NIH HHS · HL72857 · United States
NCI NIH HHS · CA114747 · United States
NHLBI NIH HHS · K08 HL076445 · United States
NHLBI NIH HHS · R01 HL072857 · United States
NHLBI NIH HHS · HL076445 · United States
NHLBI NIH HHS · R21 HL089027 · United States
NHLBI NIH HHS · R33 HL089027 · United States
NHLBI NIH HHS · HL089027 · United States
NCI NIH HHS · P50 CA114747 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0003474 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2