Embryos make myriad cell types with remarkable efficiency and reproducibility. With techniques of lineage conversion (LC) and directed differentiation (DD), researchers are now catching up in vitro, extending our understanding the process of differentiation and providing opportunities for clinical applications. Years of work have, for example, refined protocols for deriving spinal motor neurons (MNs); however, the extent to which the MNs derived from either LC or DD techniques quantitatively resemble MNs developed in vivo has remained unclear. Now, Justin Ichida, Alexander Meissner, Kevin Eggan and colleagues provide an in depth characterisation of LC and DD methods for MN derivation. They find that MNs derived from LC or DD (via either induced pluripotent stem cells or embryonic stem cells) have remarkably similar transcriptional and methylation profiles to embryonic MNs; indeed, gene ontology analysis reveals that 98% of the gene sets expressed in embryonic MNs are expressed by the DD- and LC-derived MNs. The two techniques partly differ from each other in maturation state – DD-derived MNs are more similar to immature embryonic MNs – and in expression of the clinically relevant Fas receptor, as well as the combination of Hox genes expressed. This comprehensive analysis thus reveals that LC and DD techniques are similarly successful at recapitulating how embryos make MNs, with differences that are relevant for their use in disease modelling.
