Stem Cell Lipid Organization

Funding Type: 
SEED Grant
Grant Number: 
RS1-00245
ICOC Funds Committed: 
$0
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
Cell membranes constitute one of the fundamental structural and functional elements of living organisms. These complex mixtures of lipids and proteins form the outer boundary of the cell. They distinguish between the ‘inside" and the "outside", and allow the cell to communicate with its environment and maintain its integrity. Membranes are generated when a cell is “born” and membrane lipids are continuously remodeled during the life of the cell. In this remodeling process lipids from the environment are taken up and used. All cell types in the body have a closely regulated and characteristic membrane lipid organization, and while very little is known on the lipid organization of embryonic stem cells, they are likely no exception. When stem cells are collected and grown in cell culture, it is essential to provide them with an environment that maintains their membrane integrity and allow them to proliferate and differentiate into the tissue of choice. In our proposed studies we plan to define the lipid composition and organization of stem cells in culture. We will change the cell culture conditions to modulate self-renewal and differentiation, and specifically test this in a system to where human lung epithelial cells are generated from stem cells. The biochemical, cell biology and molecular biology technology that has been established in our laboratory for cord blood derived stem cell studies will be applied for these studies on human embryonic stem cells, currently not funded by the federal government. By exploring the role of lipids in proliferation and differentiation of human embryonic stem cells, our preliminary studies will add substantially to the body of knowledge on human embryonic stem cells, and set the stage for full scale investigations to define the role of lipids in modulating the therapeutic use of embryonic stem cells.
Statement of Benefit to California: 
A significant better understanding is needed to define the powerful potential of self-renewal and differentiation of human embryonic stem cell for the diagnosis, prevention and treatment of disease and injury. While lipids are essential components of all cells, including stem cells, little is known with respect to the organization of lipids in human embryonic stem cells. Moreover, we pose that lipids in the environment of these cells may modulate both self-renewal and differentiation. We anticipate that our studies will add substantially to the body of knowledge on human embryonic stem cells, and set the stage for full scale investigations to define the role of lipids in modulating the therapeutic use of embryonic stem cells. The opportunity offered by the CIRM SEED Grant program in California allows established investigators to explore studies that would otherwise be impossible due to the lack of federal funds. Our proposed studies will be part of a large effort to establish California as an important scientific center in stem cell research. It will create a scientific community with experience in embryonic stem cell research, attract scientists interested in exploring the potential of embryonic stem cells to our state, and will accelerate the development of applications of stem cells for therapeutic use.
Progress Report: 
  • Human cells have a range of differentiation states from undifferentiated human embryonic stem cells to the terminally differentiated cells such as fibroblasts and other cells that make up the body. These differentiation states determine the functional identity of the cells to enable each cell to perform its function. Therefore, cellular differentiation is intimately linked to other cellular processes such as cell cycle and proliferation rate. In diseases such as cancer, cells become less differentiated while they gain increased capacity for autonomous cell cycling and proliferation. In stem cells, there is a balance between maintaining an undifferentiated state and regulated growth to prevent cancer formation but permit generation of progeny cells. Therefore it is important to understand how cellular differentiation is regulated. We hypothesized that epigenetic processes such as modifications of histone and other components of chromatin—the physiological form of the genome—can affect the cellular differentiation states by maintaining a stable gene expression pattern. We have found that this is indeed the case by examining the epigenetic patterns in a number of different cell types that span the range of differentiation states from different tissue types. We have found that a specific epigenetic pattern contributes to maintenance of chromatin in terminally differentiated cells representing different tissue types. Our data may inform in vitro reprogramming techniques such as iPS cell generation and have important implications for understanding how fully differentiated states are maintained in normal cells and reversed in cancer or other diseases.

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