Uncovering stem cell biology
July 30, 2009 — Vasil Galat, PhD, HCLD, with Philip M. Iannaccone, MD, PhD, of Children’s Memorial Research Center and Bert Binas of Texas A&M University have been studying extraembryonic endoderm precursor (XEN-P) cells, a type of stem cell that displays a unique molecular signature sharing some of the characteristics of embryonic stem cells, trophoblast stem cells and extraembryonic endoderm stem cells.
In a paper published Instant Online ahead of print in its original unedited form in the journal Stem Cells and Development, they demonstrate that these cells integrate not only into the visceral and parietal extraembryonic endoderm lineages as observed before, but also into the inner cell mass (ICM), the primitive endoderm, and the polar and mural trophectoderm of cultured embryos. They also show that the XEN-P cells colonize yolk sac and contribute to trophoblast lineages of post-implantation embryos following transfer to surrogate mothers. This structure comprises a heterogeneous population of cells that are loosely committed to the lineages of all parts of the developing animal.
How this state is maintained and how actual fate commitment occurs will have major implications for stem cell biology. These results raise the possibility that XEN-P cells develop from metastable precursors during ICM cellular segregation. The research team hypothesizes that the fate of precursor cells can be further modulated by culture conditions. Moreover, the cells may, to some extent, retain the capability of recommitment as seen with divergent developmental competence following integration into different compartments of the embryo. XEN-P cells provide a tool for comparative studies of different types of stem cells that can be used to improve understanding of basic stem cell biology, including pluripotency, plasticity and properties that make cells therapeutically relevant.
"The inner cell mass of the very early embryo is the source of embryonic stem cells. We now know this is a heterogeneous population of three types of cells with different potentials. Our work establishes the last of these cell types in tissue culture, allowing experiments that will help us understand how stem cells differentiate," says Galat.
Vasil Galat, PhD, HCLD is an assistant professor of Pathology at Northwestern University’s Feinberg School of Medicine; and co-directs the Children’s Memorial Research Center iPS and Human Stem Cell Core Facility with Philip M. Iannaccone, MD, PhD, who is a professor of Pediatrics and the George M. Eisenberg Professor at the Feinberg School; and senior vice president, deputy director for research and director of the Developmental Biology Program of the research center.
This research was supported in part by the Illinois Regenerative Medicine Institute, the Eisenberg Foundation for Charities, North Suburban Medical Research Junior Board and Vasil Galat’s Eisenberg Scholar Award; and the Korea Research Foundation grant to Bert Binas.
Other contributors to the work include Steven Iannaccone, Lynne-Marie Postovit, PhD and Bisrat Debeb, PhD.
Children’s Memorial Research Center is the research arm of Children's Memorial Hospital, the pediatric teaching hospital for Northwestern University's Feinberg School of Medicine. The research center is also one of 29 interdisciplinary research centers and institutes of the Feinberg School, where principal investigators who are part of the research center are full-time faculty members. Built upon a team approach, the research center generates knowledge that will lead to cures for the diseases of children with additional focus on the pediatric precursors of adult diseases. The research center actively encourages a synergy of ideas among physician scientists, basic scientists, technicians, nurses and trainees in various disciplines. Its thematic research programs bridge gaps between the biomedical, clinical and social sciences and provide an environment to accomplish common goals.
For more information contact Peggy Jones, Children’s Memorial Research Center at 773.755.6341 or pmjones@childrensmemorial.org.