Scientists Gain More New Understanding of Adult Stem Cell Regulation

By Jennifer Kelly, Innovations Report, August 8, 2007

An important mechanism for controlling the behavior of adult stem cells has been discovered by scientists at the Forsyth Institute.

Involved in cell-to-cell communication, the proteins in the flatworm, planaria, are play a novel role as researchers have observed.  The nature of the messages that control stem cell regulation may be better understood by scientists because of this research.  An example would be a message that maintains and instructs a stem cell to specialize and differentiate into a needed type of cell such as a heart cell or a lung cell.

To molecularly dissect conserved stem cell regulatory mechanisms in vivo, planarians have been recognized as a great model system in recent years.  Making them ideal for studying this process, planarians have powerful regeneration capabilities.  In order to study regeneration and development, planarians and other animal models are used by the Forsyth team.

The August 16 issue of Development will publish the Forsyth team's research.  This provides an important road map for learning about regeneration by highlighting the importance of direct cell-cell transfer of small molecules between stem cells and their neighbors explained the paper’s lead author, Néstor J. Oviedo, a postdoctoral fellow in the Forsyth Center for Regenerative and Developmental Biology.

“These findings suggest that similar mechanisms may be extraordinarily relevant for controlling the behavior of migratory, plastic cells. Further analysis in both planarians and in vertebrates will provide crucial opportunities for understanding what drives stem cell behavior and may help medical science identify novel therapeutic targets.”

During embryonic development, the left-right asymmetric positioning of the internal organs is determined by communication through gap-junctions (microscopic tunnels directly linking neighboring cells).  This was observed by the Forsyth team previously.  In this study, they turned to the role of gap junctional signals as regulators of adult stem cells in repair of injury.

As crucial signals that determine behavior of adult stem cells in vivo, Drs. Oviedo and Levin focused on direct cell-cell transfer of small molecules and ions.  Suggesting that gap junction-permeable signals are necessary to maintain tissue regeneration and stem cell state, they were able to show that the adult stem cell pool disappeared along with the regenerative capabilities when one of many specific gap junction channel types was abolished.

Promoting gap junction-mediated signaling as a new and tractable control point for adult, somatic cell regulation, this research demonstrates a novel role for gap-junction proteins.

The secreted protein factors that control embryonic stem cell differentiation has been the focus of the most recent work in the stem cell field.  However, adult/somatic stem cell behavior in vivo or in organ regeneration has never been functionally linked to a specific gap junction protein before.  This work demonstrates that gap junction channels providing direct cell-to-cell communication are a critical component for development and normal physiology.