NIH ES cell lines are 'not created equal'

A study carried out by a team of American researchers has revealed that not all embryonic stem cell (ES cell) lines are created equal. Led by UCLA's Yi Sun and Howard Hughes Medical Institute investigator Thomas Sudhof at the University of Texas Southwestern Medical Center, the study, which was published this week in the Proceedings for the National Academy of Science, compared mature neurons from two National Institute of Health (NIH) approved ES cell lines. The ES cell lines, HSF1 and HSF6, had distinct tendencies to differentiate into specific cellular types. This finding suggests that some cell lines may be more useful than others for modelling particular diseases.

The two ES cells lines were derived in similar manners and were therefore expected to differentiate into similar cellular types. This, however, was not the case. HSF1 displayed a predisposition towards generating forebrain neurons, whereas HSF6 was biased towards differentiating into neurons found in the midbrain, hindbrain, brainstem and cervical spinal cord.

Sun and her colleagues confirmed that the two ES cell lines were different by comparing the microRNAs produced by the neurons. MicroRNAs are small segments of genetic material involved in regulating cell differentiation. Sun explained that 'it's been proposed that mciroRNAs might be part of the defining signatures for human ES cells'. The team found differences in microRNA expression in the two cell lines, and suggest that these 'might contribute to this neuronal bias in the lines'.

The researchers demonstrated a new technique to generate from human ES cell lines a highly pure, large quantity of neurons. They were able to isolate the neurons and determine that they had a functional synaptic network. Since these neurons were functional it means that they can be used to model a range of neurological diseases. Sun suggested that 'by studying the chemical electrical transmissions we may be able to determine what goes wrong that leads to these debilitating diseases and find a way to stop or treat it'.

As the HSF1 line has a bias towards differentiating into forebrain neurons; it would therefore provide a better model for diseases of the forebrain, such as Huntington's Disease. 'If you're studying a disease found in a certain part of the brain, you should use a human embryonic stem cell line that produces the neurons from that region of the brain to get the most accurate results from your study', says Sun.

The researchers are now focusing on why the two cell lines have the tendencies to differentiate into different cellular types because, 'right now we don't know the causes for the functional differences we found'. Both Sun and Sudhof agree that more NIH approved stem cell lines are required to gain an understanding of the causes.