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

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

PDF(2354 KB)
PDF(2354 KB)
Protein Cell ›› 2014, Vol. 5 ›› Issue (1) : 59-68. DOI: 10.1007/s13238-013-0016-x
RESEARCH ARTICLE

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

Author information +
History +

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.

Keywords

human cardiomyocyte / DNA methylation / microarray / heart development

Cite this article

Download citation ▾
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. Protein Cell, 2014, 5(1): 59‒68 https://doi.org/10.1007/s13238-013-0016-x

References

[1]
Bauer-MehrenA, RautschkaM, SanzF, FurlongLI (2010) DisGe-NET: a Cytoscape plugin to visualize, integrate, search and analyze gene-disease networks. Bioinformatics26: 2924-2926
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[5]
DaraseliaN, YuryevA, EgorovS, NovichkovaS, NikitinA, MazoI (2004) Extracting human protein interactions from MEDLINE using a full-sentence parser. Bioinformatics20: 604-611
CrossRef Google scholar
[6]
DiepD, PlongthongkumN, GoreA, FungHL, ShoemakerR, ZhangK (2012) Library-free methylation sequencing with bisulfite padlock probes. Nat Methods9: 270-272
CrossRef Google scholar
[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
CrossRef Google scholar
[9]
JohnsonDB (1975) Finding all the elementary circuits of a directed graph. SIAM J Comput4: 77-84
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[14]
MaereS, HeymansK, KuiperM (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics21: 3448-3449
CrossRef Google scholar
[15]
MontojoJ, ZuberiK, RodriguezH, KaziF, WrightG, DonaldsonSL, MorrisQ, BaderGD (2010) GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics26: 2927-2928
CrossRef Google scholar
[16]
NovichkovaS, EgorovS, DaraseliaN (2003) MedScan, a natural language processing engine for MEDLINE abstracts. Bioinformatics19: 1699-1706
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar
[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
CrossRef Google scholar

RIGHTS & PERMISSIONS

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.
AI Summary AI Mindmap
PDF(2354 KB)

Accesses

Citations

Detail

Sections
Recommended

/