The Role of TBX3 in Human ES Cell Differentiation
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Stem cells can develop into every cell, every tissue and every organ in the human body, e.g., they can make any kind of cells in the human body. Stem cells reproduce themselves many times over and over. Their almost limitless potential has made stem cells a significant focus of medical research. But before scientists can use stem cells for medical purposes, they must first learn how to harness their power. They cannot treat disease until they learn how to manipulate stem cells to get them to develop into specific tissues or organs.
We know that turning genes on and off is crucial to the process differentiation, so we can add some factor into the culture dish and observe stem cells to differentiate into specific types of cells. But some sort of signal is needed to actually trigger the stem cells to differentiate. We are still searching for that signal. If we can ultimately learn how to direct stem cells to differentiate into one type of tissue or another, then we can use them to treat patients. In this proposal, we will first examine this step.
We propose a novel approach to understanding differentiation of human embryo stem (hES) cells, by studying TBX3, a protein called a transcription factor that controls the expression of other genes. In humans, the loss of function of TBX3 causes Ulnar-Mammary Syndrome, a genetic disorder that can pass from one generation to the next. Furthermore, our preliminary results show that TBX3 is downstream mediator of another protein, BMP4. BMP4 is a known key regulator for hES cell differentiation. Thus, TBX3 is an attractive candidate as a downstream mediator of BMP4 in hES cell differentiation. We will test TBX3 effects on hES cell differentiation if down-regulate TBX3 in hES cells with a technology called siRNA knockdown. We will identify the genes controlled by TBX3 with a recently invented powerful technology called CHIP-GLAS. This technique allows us to examine thousands of genes on a small chip in a single experiment. We expect that the innovative experiments proposed here will open a new avenue to understanding the signal of hES cell differentiation.
|Study Design:||Observational Model: Case-Only|
|Official Title:||The Role of TBX3 in Human ES Cell Differentiation|
- The cell morphology and biochemical changes will be examined for the effects of TBX3 knockdown on hES cell differentiation, including testing human ß-CG estradiol and progesterone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To identify the targets of TBX3 in BMP4-induced hES cells, we will perform ChIP-GLAS analysis. CHIP-GLAS will allow us to identify the genome-wide downstream target genes directly bound by TBX3 in hES cells. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
NIH-approved cell lines will be available at the Sue and Bill Gross Stem Cell Research Core Facility at the University of California, Irvine. Non-NIH-approved cell lines will be obtained from Sue & Bill Gross Stem Cell Core at UC Irvine.
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||August 2010|
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