However, while PPARγ is necessary and sufficient to induce the WA differentiation program, it is necessary but not sufficient for BA differentiation.
Furthermore, there was no evidence of alteration of mesoderm sub-type formed with addition of FGF1, 4 or 8. Inhibition of endogenous FGF signalling, however, prevented mesoderm and favoured neural differentiation, suggesting FGF signalling was required but not sufficient for the differentiation of primitive ectoderm into primitive streak-like intermediates.
However, these changes are not sufficient for definitive differentiation to trophectoderm (TE) in chimeric embryos.
This was confirmed by siRNA-mediated knockdown of EZH2, which only resulted in a very weak activation of the HOXA cluster (Figure 3A and S3B), indicating that EZH2 degradation is not sufficient for cellular differentiation.
Many groups have showed that Th17 cells can be induced from naïve T cells by culturing these cells with a cocktail of inflammatory cytokines such as IL-1β, IL-6 and TGFβ, and that IL-23 is necessary but not sufficient for the differentiation of Th17 cells [9] [12].
On the basis of the strong correlation found between β-casein expression and biomimetic cell elastic moduli (Supplementary Figure 5), it is conceivable that the physiological range of cellular elasticity is necessary, although not sufficient, for functional differentiation of MECs.
First, Oct4-null ES cells with constitutive expression of transfected Oct4 and overexpression of Cdx2 were differentiated into TE lineage, suggesting expression of Oct4 alone is not sufficient for blocking trophectoderm differentiation triggered by Cdx2 overexpression [34].
While our data support a collaborative role for IL-6 and IL-21 in Tfh differentiation, these cytokines are not sufficient for instruction of Tfh differentiation (Figure 3).
Previous work suggests that Mustn1 is necessary but not sufficient for chondrogenic proliferation and differentiation, as well as myogenic differentiation in vitro.
Taken together, these results indicate that reduction of Mbd3 expression is not sufficient for fully committed TE lineage differentiation.
