The Role of Heterochromatin in Stem Cell Differentiation and Reprogramming
Human development begins at fertilization when the human embryo begins to divide and differentiate. During the process of
embryo development, the totipotent embryo generates the diverse cell types that make up the organs and tissues of the adult.
As cells specialize their functions their patterns of gene expression change to support their specific roles in different tissues and
organs; for example, pancreatic cells begin to produce insulin while cardiac cells express the genes required for heart muscle
contraction. Fundamental to the specialization of different cell types are the changes that occur to control the switch in gene
expression patterns. A major component of this process is the reorganization of the cell nucleus to activate or repress different
genes. The goal of our work is to understand how stem cells change the organization of their nuclei in order to differentiate into
specific cell types.
A major research focus in stem cell biology is the generation of stem cells from adult tissues that can be used for therapeutic
purposes. These induced pluripotent cells may be ideal for stem cell based therapies because they are capable of generating the
tissues from which they were derived and they can be generated from adult tissues. The nuclear organization of stem cells is
globally open and permissive for gene expression but as stem cells differentiate they compact different regions of the genome.
During the generation of these induced pluripotent cells the genome changes its organization from the compact state of the
tissue specific cell to the open state of the stem cell. An important aspect of our proposal is to identify the molecular factors that
control genome reorganization so that we can improve the efficiency of induced pluripotent cell generation from adult tissues.
Our research has the potential to significantly improve the development of patient specific therapies based upon tissue specific
stem cell generation.
This research plan will benefit the State of California by improving the methods to generate induced pluripotent stem cells.
Improved methods for tissue and donor specific pluripotent cell generation will circumvent the problems of immune rejection of
cells and provide a patient specific therapeutic approach to disease treatment. Our experimental approach should be applicable
to any tissue type and thus should facilitate stem cell generation for a broad spectrum of diseases. Our research will further the
basic biological understanding of the processes of stem cell maintenance and cell differentiation. Insight into the biology of
stem cells will lay the groundwork for future studies and the development of novel, stem cell based, therapeutic approaches.