For example, human hematopoietic stem cells capable of multilineage hematopoietic repopulation can be purified on the basis of CD34 + expression and the absence of lineage markers, but this seemingly homogeneous population of stem cells was subsequently found to comprise cells that possess differing capabilities of multilineage repopulation, revealing the existence of short-term and long-term repopulating cells. The heterogeneity seen within the HSC population has also been observed in leukemic stem cells, which were also once considered to be homogeneous. In another example, in the intestinal crypts, stem cells were traditionally Picrinine divided into a self renewing stem cell compartment and a transit amplifying compartment. However, more recent evidence suggests that the intestinal crypt stem cell compartment can be repopulated in some circumstances by cells that had apparently converted to transit amplifying cells. The repertoire of markers available for classifying stem cells is often limited, and discrimination between classes of stem cells ultimately requires functional testing. Within the stem cell compartment there is another more subtle form of heterogeneity that is possible, whereby the cells reversibly interconvert between substates that are functionally non-equivalent while retaining the capacity for multilineage differentiation. For example, mouse ES cells are capable of switching reversibly between Nanog positive and negative states, losingand gaining expression of a gene previously Isoscopoletin proposed as a key regulator of pluripotency. Interconvertible Stella and Stella mouse ES cells have been observed and proposed to represent the switch between functionally distinct mouse ES cells and epiblast cells. Human ES cells in culture may also be divided into hierarchical subsets that nevertheless can interconvert. In one study of human ES cells, we found evidence for subsets that differentially express the surface antigen SSEA3, and hypothesised that SSEA3 and SSEA3 cells can interconvert, and that the SSEA3 cells are closer to initiating differentiation.