Epigenetic signatures direct the repair potential of reprogrammed cells

ScienceDaily (Mar. 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.

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.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Tufts University, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. K. J. Hewitt, Y. Shamis, E. Knight, A. Smith, A. Maione, A. Alt-Holland, S. D. Sheridan, S. J. Haggarty, J. A. Garlick. PDGFR? Expression and Function in Fibroblasts Derived from Pluripotent Cells is Linked to DNA Demethylation. Journal of Cell Science, 2012; DOI: 10.1242/jcs.099192

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://www.sciencedaily.com/releases/2012/03/120314124654.htm

occupy oakland morgellons disease arik armstead sag awards red carpet torrey pines nhl all star game 2012 pollyanna