An international team of investigators determined that pluripotent stem cell lines display significant chemical similarity. The cell samples used in the study all had a particular protein-protein network in common. The network, named PluriNet by the team, points to the factors that enable these cells to differentiate into multiple cell types.
Using a collection of about 150 human cell samples, the researchers created a database of global gene expression profiles using Illumina’s BeadArray technology.
“Our results offer a new strategy for classifying stem cells by their molecular machinery,” says Jeanne Loring, Ph.D., director of the Center for Regenerative Medicine at Scripps Research Institute. “We show that pluripotence and self-renewal are under tight control by specific molecular networks.”
In the first phase of the study, the group compiled transcriptional profiles from several hundred human stem cell preparations including both pluripotent stem cells and multi-potent stem cells. These included human embryonic lines, neural stem cells, mesenchymal stem cells, differentiated cell types from donors, and differentiated cells derived from pluripotent cells.
The research team coupled a computer approach with systems biology tools and found the profiles uniquely characteristic of the pluripotent populations, whether they came from embryonic stem cells or induced pluripotent cells. The researchers also found these profiles were shared by mouse embryonic stem cells, induced mouse pluripotent stem cells, and human oocytes.
Detailed analysis showed that the interacting protein elements can be used to predict whether genetically induced stem cells will be pluripotent, the scientists report.
“Stem cell preparations can now be categorized with great accuracy based on their transcriptional phenotypes without any scientists’ preconceptions or bias,” according to first author Franz-Josef Mueller, M.D., a visiting investigator at Scripps Research. Next, the researchers plan to investigate the regulation of this protein network.
Dr. Mueller was joined by scientists at Tel Aviv University, University of California, San Diego, Irvine, and Davis, Burnham Institute for Medical Research, Children's Hospital Boston, Invitrogen, Children's Hospital of Orange County Research Institute, and University Medical Center Hamburg-Eppendorf.
The study appeared on August 24 online in Nature.