All Embryonic Stem Cells Are Not Created Equal; Abraham Lincoln Would Cry

An analysis of two NIH-approved human embryonic stem-cell (ESC) lines An analysis of two NIH-approved human embryonic stem-cell (ESC) lines revealed that not all ESC lines are created equal. They each have a tendency to differentiate into specific -- but distinct -- cellular types, suggesting that some lines will be better at disease modeling than others.

Led by Howard Hughes Medical Institute (HHMI) Investigator Thomas Südhof and UCLA stem-cell biologist Yi Sun, the study also demonstrated a new technique for deriving neurons from ESCs that spontaneously form functioning neural networks under the right culture conditions. The study authors monitored the differences in the resulting neurons to confirm that ESC lines are not all alike.

The innate differentiation tendencies of the two lines (HSF1 and HSF6) expressed the most striking differences. HSF1 was predisposed toward generating forebrain neurons, whereas HSF6 displayed a bias in favor of a different variety of neurons -- including those of the midbrain, hindbrain, brainstem, and cervical spinal cord.

Both Sun and Südhof argue that their new research demonstrates the need for more NIH-approved ESC lines.

Both Sun and Südhof said that their findings have implications for the production of ES cell lines. “There is absolutely no question that these findings mean that there need to be more embryonic stem cell lines for research purposes and for use in potential treatments,” said Südhof.

Sun said that developing more ES cell lines is important “because right now we still don't know the causes for the functional differences we found. Understanding the causes will require more cell lines for study. And once we understand the causes, we can take them into account in generating new cell lines that will be better defined and enable more reproducible applications.”

The study, to be published this week in the Proceedings of the National Academy of Sciences, stated that the intrinsic differentiation potential of the HSF1 line would provide a better model than HSF6 for diseases of the forebrain, such as Huntington's.

Studying the NIH-approved lines to learn which diseases each one would best model would be a great idea. The NIH has already delayed one with a similar intent, which is unfortunate.

Not All Embryonic Stem Cell Lines Are Created Equal [HHMI]