Regulation of human embryonic stem cell fate by different forms of the Polycomb transcriptional silencing machinery.

Funding Type: 
SEED Grant
Grant Number: 
RS1-00201
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
We propose to investigate the mechanisms that maintain embryonic stem cells in the undifferentiated, pluripotent state and how those mechanisms change to allow cells to initiate the first steps of embryonic development. Work in mouse embryonic stem cells suggests that genes that will be turned on during early embryonic development are primed for expression but kept silenced by a complex of regulatory proteins termed the Polycomb group machinery (PcG). We will investigate whether different forms of the PcG machinery components are expressed in human embryonic stem cells compared to differentiating early embryonic cells and whether different forms of the PcG complex bind to and silence different target genes. Our proposed work will uncover fundamental mechanisms that allow human embryonic stem cells to grow and proliferate in the undifferentiated state while maintaining their pluripotent character. These properties are critical for the ability to expand embryonic stem cell populations in order to be able to use the cells for screens for potential therapeutic treatments (if derived from disease carrying individuals). Maintenance of the pluripotent state is also critical for expanding stem cell populations for use in possible cell based transplantation therapies. In addition, our work may reveal mechanisms that help guide early embryonic cells toward particular differentiation pathways, such as neuronal or endoderm or muscle precursors, during the early stages of development. Knowledge of these mechanisms will help in the design of strategies for inducing human embryonic stem cells to initiate differentiation into specific cell types, a key step for cell based regenerative medicine.
Statement of Benefit to California: 
The proposed research will lay important groundwork for the ability to grow and guide the differentiation of human embryonic stem cells. These capabilities underlie all ability to use embryonic stem cells for screens for therapies and for embryonic stem cell based regenerative medicine. The proposed experiments may uncover fundamental mechanisms that allow human embryonic stem cells to grow and proliferate in the undifferentiated state while maintaining their pluripotent character. Maintenance of the pluripotent state is critical for expanding stem cell populations for use in possible cell based transplantation therapies. These properties are also critical for the ability to expand embryonic stem cell populations in order to be able to use the cells for screens for potential therapeutic treatments. In addition, the proposed research may reveal mechanisms that help guide early embryonic cells toward particular differentiation pathways, such as neuronal or endoderm (precursor to pancreas and liver) or muscle precursors, during the early stages of development. Knowledge of these mechanisms will help in the design of strategies for inducing human embryonic stem cells to initiate differentiation into specific cell types, a key step for cell based regenerative medicine.

© 2013 California Institute for Regenerative Medicine