Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state

摘要: A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of subtypes, displaying differential vulnerability different neurodegenerative diseases. The ability manipulate cell subtype diversification critical establish accurate, clinically relevant vitro disease models. Retinoid signalling contributes caudal precursor specification and subsequent MN Here we investigate the necessity for retinoic acid motor neurogenesis from embryonic stem cells. We show that activin/nodal inhibition, followed by sonic hedgehog agonist treatment, sufficient specification, which occurs even presence retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent results ground state biased caudal, medial columnar identities greater retinoid-dependent diversity MNs, including those lateral columns, can be selectively derived vitro.