Protein & Cell >

2014 , Vol. 5 >Issue 1: 59 - 68

DOI: https://doi.org/10.1007/s13238-013-0016-x

RESEARCH ARTICLE

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes

  • Ying Gu 1 ,
  • Guang-Hui Liu , 2,3 ,
  • Nongluk Plongthongkum 4 ,
  • Christopher Benner 1 ,
  • Fei Yi 1 ,
  • Jing Qu 2 ,
  • Keiichiro Suzuki 1 ,
  • Jiping Yang 2 ,
  • Weiqi Zhang 2 ,
  • Mo Li 1 ,
  • Nuria Montserrat 5,6 ,
  • Isaac Crespo 7 ,
  • Antonio del Sol 7 ,
  • Concepcion Rodriguez Esteban 1 ,
  • Kun Zhang , 4 ,
  • Juan Carlos Izpisua Belmonte , 1,5
Expand
  • 1. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
  • 2. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • 3. State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • 4. Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA
  • 5. Center of Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain
  • 6. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Poeta Mariano Esquillor s/n, 50018 Sargossa, Spain
  • 7. Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Walferdange, Luxembourg

Received date: 01 Jul 2013

Accepted date: 30 Jul 2013

Published date: 01 Jan 2014

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fold

Abstract

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT+) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.

Key words： human cardiomyocyte; DNA methylation; microarray; heart development

Cite this article

Ying Gu , Guang-Hui Liu , Nongluk Plongthongkum , Christopher Benner , Fei Yi , Jing Qu , Keiichiro Suzuki , Jiping Yang , Weiqi Zhang , Mo Li , Nuria Montserrat , Isaac Crespo , Antonio del Sol , Concepcion Rodriguez Esteban , Kun Zhang , Juan Carlos Izpisua Belmonte . Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes[J]. Protein & Cell, 2014 , 5(1) : 59 -68 . DOI: 10.1007/s13238-013-0016-x

References

Publishing order | Descend order by publishing year | Descend order by cited within
1
Bauer-MehrenA, RautschkaM, SanzF, FurlongLI (2010) DisGe-NET: a Cytoscape plugin to visualize, integrate, search and analyze gene-disease networks. Bioinformatics26: 2924-2926

DOI

2
BeqqaliA, KlootsJ, Ward-van OostwaardD, MummeryC, PassierR (2006) Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells24: 1956-1967

DOI

3
CaoF, WagnerRA, WilsonKD, XieX, FuJD, DrukkerM, LeeA, LiRA, GambhirSS, WeissmanIL (2008) Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS One3: e3474

DOI

4
CrespoI, KrishnaA, Le BechecA, del SolA (2013) Predicting missing expression values in gene regulatory networks using a discrete logic modeling optimization guided by network stable states. Nucleic Acids Res41: e8

DOI

5
DaraseliaN, YuryevA, EgorovS, NovichkovaS, NikitinA, MazoI (2004) Extracting human protein interactions from MEDLINE using a full-sentence parser. Bioinformatics20: 604-611

DOI

6
DiepD, PlongthongkumN, GoreA, FungHL, ShoemakerR, ZhangK (2012) Library-free methylation sequencing with bisulfite padlock probes. Nat Methods9: 270-272

DOI

7
GargA, XenariosI, MendozaL, DeMicheliG (2007) Lecture notes in computer science vol. 4453. In: Speed T, Huang H (eds). Springer, Berlin, p62-76

8
GargA, Di CaraA, XenariosI, MendozaL, De MicheliG (2008) Synchronous versus asynchronous modeling of gene regulatory networks. Bioinformatics24: 1917-1925

DOI

9
JohnsonDB (1975) Finding all the elementary circuits of a directed graph. SIAM J Comput4: 77-84

DOI

10
KattmanSJ, WittyAD, GagliardiM, DuboisNC, NiapourM, HottaA, EllisJ, KellerG (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell8: 228-240

DOI

11
LianX, HsiaoC, WilsonG, ZhuK, HazeltineLB, AzarinSM, RavalKK, ZhangJ, KampTJ, PalecekSP (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA109: E1848-E1857

DOI

12
LiuGH, BarkhoBZ, RuizS, DiepD, QuJ, YangSL, PanopoulosAD, SuzukiK, KurianL, WalshC (2011) Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature472: 221-225

DOI

13
LiuGH, QuJ, SuzukiK, NivetE, LiM, MontserratN, YiF, XuX, RuizS, ZhangW (2012) Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature491: 603-607

DOI

14
MaereS, HeymansK, KuiperM (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics21: 3448-3449

DOI

15
MontojoJ, ZuberiK, RodriguezH, KaziF, WrightG, DonaldsonSL, MorrisQ, BaderGD (2010) GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics26: 2927-2928

DOI

16
NovichkovaS, EgorovS, DaraseliaN (2003) MedScan, a natural language processing engine for MEDLINE abstracts. Bioinformatics19: 1699-1706

DOI

17
PaigeSL, ThomasS, Stoick-CooperCL, WangH, MavesL, SandstromR, PabonL, ReineckeH, PrattG, KellerG (2012) A temporal chromatin signature in human embryonic stem cells identifies regulators of cardiac development. Cell151: 221-232

DOI

18
ShannonP, MarkielA, OzierO, BaligaNS, WangJT, RamageD, AminN, SchwikowskiB, IdekerT (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res13: 2498-2504

DOI

19
SynnergrenJ, AkessonK, DahlenborgK, VidarssonH, AmeenC, SteelD, LindahlA, OlssonB, SartipyP (2008) Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells. Stem Cells26: 1831-1840

DOI

20
WillemsE, Cabral-TeixeiraJ, SchadeD, CaiW, ReevesP, BushwayPJ, LanierM, WalshC, KirchhausenT, Izpisua BelmonteJC (2012) Small molecule-mediated TGF-beta type II receptor degradation promotes cardiomyogenesis in embryonic stem cells. Cell Stem Cell11: 242-252

DOI

21
XieW, SchultzMD, ListerR, HouZ, RajagopalN, RayP, WhitakerJW, TianS, HawkinsRD, LeungD (2013) Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell153: 1134-1148

DOI

22
YangL, SoonpaaMH, AdlerED, RoepkeTK, KattmanSJ, KennedyM, HenckaertsE, BonhamK, AbbottGW, LindenRM (2008) Human cardiovascular progenitor cells develop from a KDR+embryonic-stem-cell-derived population. Nature453: 524-528

DOI

23
ZhangJ, KlosM, WilsonGF, HermanAM, LianX, RavalKK, BarronMR, HouL, SoerensAG, YuJ (2012) Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells: the matrix sandwich method. Circ Res111: 1125-1136

DOI

Options
Outlines

/

〈 〉