Neurons of the mouse hippocampus FLICKR, NICHDResearchers now recognize that there is far more heterogeneity within a given cell type than previously appreciated. Perhaps nowhere in the body is this more striking than in the brain. But as new technologies reveal differences in the genome, epigenome, and transcriptome of cells, we now must wrestle with the question of how to define cell types.
Previous approaches to cell-type identification were based on identifying the presence of a small set of known markers. Current high-throughput, single-cell sequencing methods, on the other hand, enable quantifiable cell-type classification with little or no prior knowledge, revealing previously unidentified variations in cellular phenotypes across numerous tissue types. But, given that cells do not cluster perfectly into distinct units, what portion of this heterogeneity truly defines a novel cell type and what portion can instead be attributed to variations in cell state or to methodological artifacts?
In practice, these single-cell experiments analyze thousands of cells, often with sets of 40,000+ genetic predictors; therefore, it is tempting to perform stratification after stratification to continually identify new cell types, resulting in groupings that go far beyond “type” ...
