Cardiac myocyte differentiation: The Nkx2.5 and Cripto target genes in P19 clone 6 cells

Hailing Liu, Thomas M. Harris, Hyung H. Kim, Geoffrey J. Childs

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Genetic evidence has implicated several genes as being critical for the development of cardiomyocytes. Whereas a few of the targets of these genes and the pathways they constitute are known the majority of targets and the interrelationships of the pathways involved still remains largely unknown. The power of high-throughput analytical techniques like microarrays and real-time RT-PCR combined with the ability to selectively silence specific mRNA in model tissue culture systems can begin to fill in these gaps and increase our understanding of the molecular mechanisms of cell commitment and terminal differentiation. We have used microarray analysis and siRNA directed against the cardiac-specific transcription factor Nkx2.5 and one of its targets Cripto in P19 clone 6 (P19Cl6) cells to identify potential targets for these genes. We demonstrate Nkx2.5 affects genes that have been shown to be controlled by the canonical Wnt or TGFβ/BMP signaling pathways. We also show that Cripto can regulate the critical stem cell gene Nanog and two Oct 4-regulated genes: Dppa2 and 4. Cripto also affects the formation of nitric oxide, a small signaling molecule that has been reported to be important for growth and development of cardiac and smooth muscle. It affects the nitric oxide system by regulating genes that control the levels of nitric oxide synthase mRNA concentration as well as the activation and bioavailability of the protein.

Original languageEnglish (US)
Pages (from-to)218-239
Number of pages22
JournalFunctional and Integrative Genomics
Volume5
Issue number4
DOIs
StatePublished - Oct 2005

Fingerprint

Cardiac Myocytes
Clone Cells
Genes
Nitric Oxide
Messenger RNA
Microarray Analysis
Growth and Development
Nitric Oxide Synthase
Small Interfering RNA
Biological Availability
Smooth Muscle
Real-Time Polymerase Chain Reaction
Myocardium
Transcription Factors
Stem Cells
Proteins

Keywords

  • Cardiomyocyte differentiation
  • Microarray
  • P19 clone 6 cells
  • RNAi

ASJC Scopus subject areas

  • Genetics

Cite this

Cardiac myocyte differentiation : The Nkx2.5 and Cripto target genes in P19 clone 6 cells. / Liu, Hailing; Harris, Thomas M.; Kim, Hyung H.; Childs, Geoffrey J.

In: Functional and Integrative Genomics, Vol. 5, No. 4, 10.2005, p. 218-239.

Research output: Contribution to journalArticle

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