Cautiously Interpret Data

I was troubled to see the work of Injae Shin, entitled "Imidazole Spurs Neurogenesis," highlighted in the Science & Technology Concentrates without any qualifications (C&EN, July 16, page 28). His findings propose to overturn years of work in the field of developmental biology, claiming that a small molecule can transdifferentiate mouse myoblasts into neurons, a conversion between cell lineages that arise from different germ layers during development.

Though the claim is exciting, the experimental evidence supporting the claim is very preliminary. A reasonable alternative explanation for the observed data is cellular mimicry, the phenomenon when one cell type morphologically appears like another without possessing any of the functions that make it unique from all other cell types. Past examples of this are well-documented, and countless commentaries and entire reviews have been published by developmental biologists warning against such misinterpretations.

Although immunostaining and dye endocytosis are consistent with the formation of neurons, they certainly do not provide demonstrative proof. More definitive techniques are required to properly characterize a cell's true lineage. For example, the cells should be assayed for the gain and loss of lineage markers by more specific experiments (i.e., qRT-PCR) and tested for cell-specific functions (i.e., voltage clamping). It should be noted that Shin et al. did make an attempt to analyze the gene expression profile of the treated cells. However, their microarray analysis only identified 20–30 genes that exhibit differential expression, none of which are exclusively expressed in neurons.

Moreover, the expression profile was not compared to real neurons. Comparison to primary cells is absolutely necessary and needs to be done in every assay where in vivo function is required to conclusively demonstrate the true lineage of the cells in question. Although the work of Shin may ultimately prove to be an exciting new discovery, I have observed similar morphological and immunochemical changes induced by small molecules that were not a result of lineage switching.

In conclusion, chemists need to be very careful when entering complex fields such as stem cell biology, because profound assertions can be made (in some cases, based on in vitro data). The data published in chemical journals may not be reviewed by experts in that particular field (likewise with biologists publishing chemistry in Cell). Under these circumstances, one should be cautious when interpreting data until all conclusive experiments are completed.

Costas Lyssiotis
La Jolla, Calif.