Figure 1

Energy landscape models for iPSC reprogramming. (a) Illustration of the energy landscape experienced by cells under reprogramming conditions. The funnel-like energy landscape represents the path from somatic cell states (for example, MEF and GMP) at the boundaries of the funnel, to the pluripotent state at the middle lowest energy point. (b) Energy plot of the path from MEF to iPSC under different epigenetic perturbations. The black line represents the energy landscape experienced by wild-type MEFs. The red line represents the energy landscape experienced by Mbd3-depleted (Mbd3^low) MEF donor cells. This depletion reduces energy barriers and accelerates reprogramming by OSKM to a near-deterministic process. Notably, imposed barriers can occur by depletion of non-rate-limiting essential factors, such as Utx and Wdr5 epiegentic reegulators, whose depletion inhibits and impairs the reactivation of pluripotency genes by OSKM, as marked by the imposed dashed black line barriers [2]. (c) Energy plot of the path from MEF (black line) or GMP (blue line) states to the iPSC state. Energy peaks represent barriers in the reprogramming path, where higher barriers correspond with low conversion rates. Different cell types experienced different barrier landscapes [4]. GMP, granulocyte monocyte progenitor; iPSC, induced pluripotent stem cell; MEF, mouse embryonic fibroblast; Mbd3, methyl-CpG-binding domain protein 3; OSKM, Oct4, Sox2, Klf4 and Myc.