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The Role of TBX3 in Human ES Cell Differentiation

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ClinicalTrials.gov Identifier: NCT00581152
Recruitment Status : Unknown
Verified December 2007 by University of California, Irvine.
Recruitment status was:  Active, not recruiting
First Posted : December 27, 2007
Last Update Posted : December 27, 2007
Sponsor:
Collaborator:
CIRM SEED Grant
Information provided by:
University of California, Irvine

Study Description
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Brief Summary:

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.


Condition or disease
TBX3 Cell Differentiation

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Study Design
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Study Type : Observational
Estimated Enrollment : 4 participants
Observational Model: Case-Only
Official Title: The Role of TBX3 in Human ES Cell Differentiation
Study Start Date : August 2007
Estimated Study Completion Date : August 2010
Groups and Cohorts
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information


Outcome Measures
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

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.

Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
No subjects will be consented for this study. Approximately 2 to 4 cell lines will be collected.
Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations
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No Contacts or Locations Provided
More Information
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Taosheng Huang, M.D., Ph.D, University of California, Irvine
ClinicalTrials.gov Identifier: NCT00581152     History of Changes
Other Study ID Numbers: OCRT07015
HS# 2007-5848
First Posted: December 27, 2007    Key Record Dates
Last Update Posted: December 27, 2007
Last Verified: December 2007

Keywords provided by University of California, Irvine:
TBX3