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Article: Dynamic MicroRNA expression programs during cardiac differentiation of human embryonic stem cells: Role for miR-499
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TitleDynamic MicroRNA expression programs during cardiac differentiation of human embryonic stem cells: Role for miR-499
 
AuthorsWilson, KD1 1
Hu, S1
Venkatasubrahmanyam, S1
Fu, JD4
Sun, N1
Abilez, OJ1 1
Baugh, JJA1
Jia, F1
Ghosh, Z1
Li, RA4 2
Butte, AJ1
Wu, JC1 3
 
KeywordsCardiomyocyte
Differentiation
Heart
Human embryonic stem cells
Microarrays
MicroRNA
 
Issue Date2010
 
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circgenetics.ahajournals.org/
 
CitationCirculation: Cardiovascular Genetics, 2010, v. 3 n. 5, p. 426-435 [How to Cite?]
DOI: http://dx.doi.org/10.1161/CIRCGENETICS.109.934281
 
AbstractBackground-MicroRNAs (miRNAs) are a newly discovered endogenous class of small, noncoding RNAs that play important posttranscriptional regulatory roles by targeting messenger RNAs for cleavage or translational repression. Human embryonic stem cells are known to express miRNAs that are often undetectable in adult organs, and a growing body of evidence has implicated miRNAs as important arbiters of heart development and disease. Methods and Results-To better understand the transition between the human embryonic and cardiac "miRNA-omes," we report here the first miRNA profiling study of cardiomyocytes derived from human embryonic stem cells. Analyzing 711 unique miRNAs, we have identified several interesting miRNAs, including miR-1, -133, and -208, that have been previously reported to be involved in cardiac development and disease and that show surprising patterns of expression across our samples. We also identified novel miRNAs, such as miR-499, that are strongly associated with cardiac differentiation and that share many predicted targets with miR-208. Overexpression of miR-499 and -1 resulted in upregulation of important cardiac myosin heavy-chain genes in embryoid bodies; miR-499 overexpression also caused upregulation of the cardiac transcription factor MEF2C. Conclusions-Taken together, our data give significant insight into the regulatory networks that govern human embryonic stem cell differentiation and highlight the ability of miRNAs to perturb, and even control, the genes that are involved in cardiac specification of human embryonic stem cells. © 2010 American Heart Association, Inc.
 
DescriptionComment in Circ Cardiovasc Genet. 2011 Feb 1;4(1):e3; author reply e4.
 
ISSN1942-325X
2012 Impact Factor: 6.728
 
DOIhttp://dx.doi.org/10.1161/CIRCGENETICS.109.934281
 
PubMed Central IDPMC3057038
 
ISI Accession Number IDWOS:000283163100006
Funding AgencyGrant Number
Stanford Bio-X Fellowship
National Institutes of HealthDP2 OD004437
HL099776
HL089027
CIRMRC1-00151-1
BWF
Funding Information:

This work was supported by a Stanford Bio-X Fellowship (to K.D.W.), CIRM RC1-00151-1 (O.J.A. and J.J.A.B.), and National Institutes of Health grants DP2 OD004437, HL099776, HL089027, and BWF (to J.C.W.).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWilson, KD
 
dc.contributor.authorHu, S
 
dc.contributor.authorVenkatasubrahmanyam, S
 
dc.contributor.authorFu, JD
 
dc.contributor.authorSun, N
 
dc.contributor.authorAbilez, OJ
 
dc.contributor.authorBaugh, JJA
 
dc.contributor.authorJia, F
 
dc.contributor.authorGhosh, Z
 
dc.contributor.authorLi, RA
 
dc.contributor.authorButte, AJ
 
dc.contributor.authorWu, JC
 
dc.date.accessioned2010-10-31T11:08:02Z
 
dc.date.available2010-10-31T11:08:02Z
 
dc.date.issued2010
 
dc.description.abstractBackground-MicroRNAs (miRNAs) are a newly discovered endogenous class of small, noncoding RNAs that play important posttranscriptional regulatory roles by targeting messenger RNAs for cleavage or translational repression. Human embryonic stem cells are known to express miRNAs that are often undetectable in adult organs, and a growing body of evidence has implicated miRNAs as important arbiters of heart development and disease. Methods and Results-To better understand the transition between the human embryonic and cardiac "miRNA-omes," we report here the first miRNA profiling study of cardiomyocytes derived from human embryonic stem cells. Analyzing 711 unique miRNAs, we have identified several interesting miRNAs, including miR-1, -133, and -208, that have been previously reported to be involved in cardiac development and disease and that show surprising patterns of expression across our samples. We also identified novel miRNAs, such as miR-499, that are strongly associated with cardiac differentiation and that share many predicted targets with miR-208. Overexpression of miR-499 and -1 resulted in upregulation of important cardiac myosin heavy-chain genes in embryoid bodies; miR-499 overexpression also caused upregulation of the cardiac transcription factor MEF2C. Conclusions-Taken together, our data give significant insight into the regulatory networks that govern human embryonic stem cell differentiation and highlight the ability of miRNAs to perturb, and even control, the genes that are involved in cardiac specification of human embryonic stem cells. © 2010 American Heart Association, Inc.
 
dc.description.naturelink_to_OA_fulltext
 
dc.descriptionComment in Circ Cardiovasc Genet. 2011 Feb 1;4(1):e3; author reply e4.
 
dc.identifier.citationCirculation: Cardiovascular Genetics, 2010, v. 3 n. 5, p. 426-435 [How to Cite?]
DOI: http://dx.doi.org/10.1161/CIRCGENETICS.109.934281
 
dc.identifier.doihttp://dx.doi.org/10.1161/CIRCGENETICS.109.934281
 
dc.identifier.epage435
 
dc.identifier.hkuros182829
 
dc.identifier.isiWOS:000283163100006
Funding AgencyGrant Number
Stanford Bio-X Fellowship
National Institutes of HealthDP2 OD004437
HL099776
HL089027
CIRMRC1-00151-1
BWF
Funding Information:

This work was supported by a Stanford Bio-X Fellowship (to K.D.W.), CIRM RC1-00151-1 (O.J.A. and J.J.A.B.), and National Institutes of Health grants DP2 OD004437, HL099776, HL089027, and BWF (to J.C.W.).

 
dc.identifier.issn1942-325X
2012 Impact Factor: 6.728
 
dc.identifier.issue5
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3057038
 
dc.identifier.pmid20733065
 
dc.identifier.scopuseid_2-s2.0-78649366701
 
dc.identifier.spage426
 
dc.identifier.urihttp://hdl.handle.net/10722/125039
 
dc.identifier.volume3
 
dc.languageeng
 
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circgenetics.ahajournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofCirculation: Cardiovascular Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshCell Differentiation - physiology
 
dc.subject.meshEmbryonic Stem Cells - cytology - physiology
 
dc.subject.meshGene Expression Regulation
 
dc.subject.meshHeart - embryology - growth and development
 
dc.subject.meshMicroRNAs - genetics - metabolism
 
dc.subjectCardiomyocyte
 
dc.subjectDifferentiation
 
dc.subjectHeart
 
dc.subjectHuman embryonic stem cells
 
dc.subjectMicroarrays
 
dc.subjectMicroRNA
 
dc.titleDynamic MicroRNA expression programs during cardiac differentiation of human embryonic stem cells: Role for miR-499
 
dc.typeArticle
 
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Author Affiliations
  1. Stanford University
  2. The University of Hong Kong
  3. Stanford University School of Medicine
  4. Mount Sinai School of Medicine