Mouse ES cell–derived cardiac precursor cells are multipotent and facilitate identification of novel cardiac genes
Nicolas Christoforou, … , Andrew S. McCallion, John D. Gearhart
Nicolas Christoforou, … , Andrew S. McCallion, John D. Gearhart
Published February 1, 2008
Citation Information: J Clin Invest. 2008;118(3):894-903. https://doi.org/10.1172/JCI33942.
View: Text | PDF
Research Article Cardiology

Mouse ES cell–derived cardiac precursor cells are multipotent and facilitate identification of novel cardiac genes

Abstract

Although the differentiation of ES cells to cardiomyocytes has been firmly established, the extent to which corresponding cardiac precursor cells can contribute to other cardiac populations remains unclear. To determine the molecular and cellular characteristics of cardiac-fated populations derived from mouse ES (mES) cells, we isolated cardiac progenitor cells (CPCs) from differentiating mES cell cultures by using a reporter cell line that expresses GFP under the control of a cardiac-specific enhancer element of Nkx2-5, a transcription factor expressed early in cardiac development. This ES cell–derived CPC population initially expressed genetic markers of both stem cells and mesoderm, while differentiated CPCs displayed markers of 3 distinct cell lineages (cardiomyocytes, vascular smooth muscle cells, and endothelial cells) — Flk1 (also known as Kdr), c-Kit, and Nkx2-5, but not Brachyury — and subsequently expressed Isl1. Clonally derived CPCs also demonstrated this multipotent phenotype. By transcription profiling of CPCs, we found that mES cell–derived CPCs displayed a transcriptional signature that paralleled in vivo cardiac development. Additionally, these studies suggested the involvement of genes that we believe were previously unknown to play a role in cardiac development. Taken together, our data demonstrate that ES cell–derived CPCs comprise a multipotent precursor population capable of populating multiple cardiac lineages and suggest that ES cell differentiation is a valid model for studying development of multiple cardiac-fated tissues.

Authors

Nicolas Christoforou, Ronald A. Miller, Christine M. Hill, Chunfa C. Jie, Andrew S. McCallion, John D. Gearhart

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (1.97 MB)

Advertisement