Epigenetic regulation of human cardiac differentiation

Epigenetic regulation of human cardiac differentiation

Funding Type: 
Basic Biology IV
Grant Number: 
RB4-05901
Award Value: 
$1,708,560
Disease Focus: 
Heart Disease
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Status: 
Active
Public Abstract: 
Each cell type in our body has its own identity. This identity allows a heart cell to contract repetitively, and a brain cell to conduct nerve impulses. Each cell type gains its identity by turning on or off thousands of genes that together give the cell its identity. Understanding how these sets of genes are regulated together as a cell gains its identity is important to be able to generate new cells in disease. For example, after a heart attack, heart muscle dies, leaving scar tissue and a poorly functioning heart. It would be very useful to be able to make new heart muscle by introducing the right set of instructions into other cells in the heart, and turn them into new heart muscle cells. One way that many genes are turned on or off together is by a cellular mechanism called epigenetic regulation. This global regulation coordinates thousands of genes. We plan to understand the epigenetic regulatory mechanisms that give a human heart muscle cell its identity. Understanding their epigenetic blueprint of cardiac muscle cells will help develop strategies for cardiac regeneration, and for a deeper understanding of how cells in our body acquire their individual identities and function.
Statement of Benefit to California: 
This research will benefit the state of California and its citizens by helping develop new approaches to cardiac regeneration that will be more efficient than current approaches, and amenable to drug-based approaches. In addition, the knowledge acquired in these studies will be important not only for heart disease, but for any other disease where reprogramming to regenerate new cells is desirable. The mechanisms revealed by this research will also lead to new understanding of the basis for congenital heart defects, which affect several thousand Californian children every year, and for which we understand very little.
Progress Report: 

Year 1

We have made considerable progress on this project, which is aimed at understanding how genes are controlled during the conversion of human stem cells into heart cells. We have been able to use advanced techniques that allow us to make millions of human heart cells in a dish from "Induced Pluripotent Stem Cells" (known as iPS cells), which are cells derived from skin cells that have properties of embryonic stem cells. We are now using genome engineering techniques to insert a mutation that is associated with human congenital heart defects. We are now starting to map the chromatin marks that will tell us how heart genes are turned on, while genes belonging to other cell types are kept off. This "blueprint" of a heart cell will help us understand how to make better heart cells to repair injured hearts, and will allow us to model human congenital heart disease in a human experimental system.

© 2013 California Institute for Regenerative Medicine