Pathway decision-making strategies for generating pancreatic beta-cells: systems biology or hit and miss?
OBJECTIVE
Method selection strategies to achieve beta-cell differentiation from human embryonic stem cells are reviewed.


RESULTS
Expectations are high for an embryonic stem cell derived cellular replacement method to cure diabetes, and recent observations indicate that mature beta-cells can be derived from human embryonic stem cells. In terms of the translational setting, however, we are not there yet; conversion of embryonic stem cells to fully mature beta-cells is not effective and does not provide an exclusive beta-cell population as the end-product.


CONCLUSIONS
Studies emphasize that expecting development of a 'magic media bullet' that promotes endocrine fate is rather optimistic; consecutive administration of signaling inducers, carefully provided to mimic normal development, is more likely to succeed. To accomplish this task we need better understanding of the extracellular signaling pathways that drive progressive endodermal fate choices throughout development. Knowledge of cell-intrinsic control of fate assignments in pancreas is growing rapidly. Nevertheless, insufficient information regarding morphogen codes that operate in endoderm and pancreas is hindering development of better, directed differentiation schema of uncommitted embryonic stem cells toward endodermal, pancreatic, and subsequent endocrine specific fates. A systematic approach to defining morphogen codes in developing endoderm and pancreas appears timely and justified.
Jensen
Jan
J
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, Colorado, USA. jan.jensen@uchsc.edu
D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D010179:Pancreas / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction; D049490:Systems Biology