Analysis of the Mode of Division of Human Embryonic Stem Cells

Funding Type: 
SEED Grant
Grant Number: 
RS1-00259
ICOC Funds Committed: 
$0
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Public Abstract: 
Stem cells are mater cells from which specialized cells and tissues in our body are derived. Stem cells have the ability to regenerate them (self-renewal) and at the same time produce specialized cells (differentiation). Diseases such as cancer can arise when the control of stem cell self-renewal and differentiation goes awry. How the stem cells in our body balance these tasks is not understood. Studies of stem cell behavior in other organisms have identified a number of molecules that regulate the self-renewal and differentiation of stem cells. Many of these molecules are conserved in humans. Whether there is a functional conservation is not known. The goal of this proposal is to test whether conserved mechanisms are used to control stem cell behavior in our body. Information to be obtained from this study has the potential to promote new ways to maintain human stem cells in its multipotent state in culture for long term and to direct their differentiation into specialized cells such as neurons, bone marrow cells, and heart cells, which can be used in transplantation therapies. More excitingly, this knowledge could be used to manipulate the capacity of the resident stem cells in our body to repair or re-grow damaged cell lost to disease or injury. This could revolutionize the ways doctors treat a wide range of devastating diseases such as cancer, heart disease, diabetes, autoimmune, and neurodegenerative diseases.
Statement of Benefit to California: 
Stem cells are unspecialized cells that are capable of reproducing themselves over an extended period of time. Under certain conditions, they can be transformed into cells with specialized functions. Stem cells offer the possibility of a renewable source of replacement cells and tissues to treat diseases or conditions such as Parkinson’s, Alzheimer’s, heart disease, diabetes, or spinal cord injuries. To realize the vast potential of human stem cells, we need to have a better understanding of the mechanisms that control their ability to regenerate themselves and at the same time produce specialized cells. The goal of this proposal is to identify molecules that control these unique properties of human stem cells. Information to be obtained from this study could be used to devise ways to faithfully maintain human stem cells in culture for long term and to direct their transformation into specialized cells such as neurons, bone marrow cells, and heart cells for transplantation therapies. This knowledge could also be used to harness the innate capacity of the stem cells in our body to repair or re-grow damaged cell lost to disease or injury. This could lead to new treatment strategies for a wide range of devastating diseases. Thus, the proposed research has the potential to benefit the State of California and its citizens in several ways: 1. It could lead to new cures for cancer, heart disease, diabetes, and neurodegenerative diseases. 2. It could save people's lives and cut health care costs. 3. It could stimulate growth of the biotech industry in California, thus generating new tax revenue for California.
Progress Report: 
  • We made tremendous progress on our aims related to this project. We began the grant period having never worked with human embryonic stem cells (hESCs). We ended the project period having published 3 scientific papers in high profile journals (PNAS, Cell Stem Cell, Stem Cells) covering various aspects of this work as outlined in the grant. In addition, at least two more papers will be published in the next year related to this work.
  • To summarize the work, we employed hESCs to model the development of pluripotent cells from undifferentiated "embryonic-like" cells to neural stem cells to neuronal progenitors to committed neurons and finally to fully active mature neurons. Furthermore, we developed methods to purify these cells at each step in order to determine their gene expression profile. We have made fascinating observations of changes in gene expression in these cells as they go from embryonic to fully mature neurons. The simplest way to describe this method is that we have modeled the development of a human tissue in vitro, which, without the use of hESCs would normally be impossible. As a result, we now know more about how these cells development than ever before. With this knowledge in hand, we can now test hypotheses about how neurons develop in the embryo in vitro.
  • How will these results be applied in the future? Because we now have a basic framework by which human motor neurons develop in vitro, we can attempt to affect this process by boosting or ablating expression of those genes that are induced during maturation. This will tells us which genes play a functional role in this process and perhaps hint towards future therapies for motor neuron diseases.

© 2013 California Institute for Regenerative Medicine