Public Release:  Epigenetic signatures direct the repair potential of reprogrammed cells

Tufts University, Health Sciences Campus

BOSTON (March 14, 2012) -- A research team has identified epigenetic signatures, markers on DNA that control transient changes in gene expression, within reprogrammed skin cells. These signatures can predict the expression of a wound-healing protein in reprogrammed skin cells or induced pluripotent stem cells (iPSCs), cells that take on embryonic stem cell properties. Understanding how the expression of the protein is controlled brings us one step closer to developing personalized tissue regeneration strategies using stem cells from a patient, instead of using human embryonic stem cells. The study was published in the Journal of Cell Science.

When skin cells are reprogrammed, many of their cellular properties are recalibrated as they aquire stem cell properties and then are induced to become skin cells again. In order for these "induced" stem cells to be viable in treatment for humans (tissue regeneration, personalized wound healing therapies, etc.), researchers need to understand how they retain or even improve their characteristics after they are reprogrammed.

Since the initial discovery of reprogramming, scientists have struggled with the unpredictability of the cells due to the many changes that occur during the reprogramming process. Classifying specific epigenetic signatures, as this study did, allows researchers to anticipate ways to produce cell types with optimal properties for tissue repair while minimizing unintended cellular abnormalities.

The researchers used reprogrammed cells to generate three-dimensional connective tissue that mimics an in vivo wound repair environment. To verify the role of the protein (PDGFRbeta) in tissue regeneration and maintenance, the team blocked its cellular expression, which impaired the cells' ability to build tissue.

"We determined that successful tissue generation is associated with the expression of PDGFRbeta. Theoretically, by identifying the epigenetic signatures that indicate its expression, we can determine the reprogrammed cells' potential for maintaining normal cellular characteristics throughout development," said first author Kyle Hewitt, PhD, a graduate of the cell, molecular & developmental biology program at the Sackler School of Graduate Biomedical Sciences, and postdoctoral associate in the Garlick laboratory at Tufts University School of Dental Medicine (TUSDM).

"The ability to generate patient-specific cells from the reprogrammed skin cells may allow for improved, individualized, cell-based therapies for wound healing. Potentially, these reprogrammed cells could be used as a tool for drug development, modeling of disease, and transplantation medicine without the ethical issues associated with embryonic stem cells," said senior author Jonathan Garlick, DDS, PhD, a professor in the department of oral and maxillofacial pathology and director of the division of tissue engineering and cancer biology at TUSDM.

Jonathan Garlick is also a member of the cell, molecular & developmental biology program faculty at the Sackler School and the director of the Center for Integrated Tissue Engineering (CITE) at TUSDM.

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Additional authors of the study are Yulia Shamis, MSc, a PhD candidate in the cell, molecular, and developmental biology program at the Sackler School; Elana Knight, BSc, and Avi Smith, BA, both research technicians in the Garlick laboratory; Anna Maione, a PhD student in the cell, molecular & developmental biology program at the Sackler School, and Addy Alt-Holland, PhD, MSc, assistant professor at TUSDM.

This work was supported by grant # DE017413 to Dr. Garlick from the National Institute for Dental and Craniofacial Research, part of the National Institutes of Health.

Hewitt KJ, Shamis Y, Knight E, Smith A, Maione A, Alt-Holland A, Garlick JA. Journal of Cell Science. "PDGFRbeta Expression and Function in Fibroblasts Derived from Pluripotent Cells is Linked to DNA Demethylation" Published online February 17, 2012, doi: 10.1242/jcs.099192.

About Tufts University School of Dental Medicine

Founded in 1868, Tufts University School of Dental Medicine (TUSDM) is committed to leadership in education, patient care, research and community service. Students obtain an interdisciplinary education, integrated with medicine, with access to training in dental specialties. Clinics managed at TUSDM provide quality comprehensive care to more than 18,000 diverse individuals annually, including those requiring special needs. Nationally and internationally, the School promotes health and educational programs and researches new procedures, materials and technologies to improve oral health.

About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences

Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.

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