As expected, hypertrophy and terminal differentiation was not documented early on (day 7) (Fig. 3a and Table 5).
It was expected that differences in regionally specific molecular background and/or terminal differentiation might be reflected in patterns characterizing selectively some nuclei across the major clusters, or superficial/lateral versus deep or intermediate paramedian serotonin cells across several rhombomeres.
In contrast, genes in the network involved in terminal differentiation processes, like pigment formation, are expected to produce small-scale variants, be more labile during evolution, and are associated with microevolution [ 99, 100].
As expected, cardiac specific markers (αMHC, ANF) appeared by day 14 and persisted through terminal differentiation into beating EBs.
We have also included terminal differentiation into peripheral blood and the effects of sampling on the expected clone size distribution.
It is reasonable to expect that sustained over-expression of the transgenes used to induce pluripotency might interfere with terminal differentiation and the data presented in Figure 2B, showing maintenance of Klf4 gene expression in heterogenous unselected cultures following differentiation, would support this.
The mechanism described here may be more general than expected and could account for how murine cells after fate commitment like the secretory-committed cells defer for long periods their terminal differentiation (Buczacki et al, 2013).
Different strategies have been proposed to inhibit terminal differentiation but nowadays no hyaline cartilage regeneration can be obtained in vitro, yet, and therefore no hyaline cartilage may be expected in vivo (Hellingman et al. 2012).
Furthermore, as expected, IL-1β-treated mature chondrocytes significantly produce senescence-associated secretory factors such as MMP1 and MMP13, two markers normally associated with chondrocyte terminal differentiation onset and IL-6 and IL-8, two pro-inflammatory cytokines.
Hu, J. et al. From the cover: neutralization of terminal differentiation in gliomagenesis.
