Generation of human iPSC-derived motor neurons with defined regional identities across the rostrocaudal axis

A three-protocol pipeline generates hindbrain/rhombomere-, cervical-, and lumbar-region human iPSC-derived motor neurons with graded rostrocaudal identity and region-matched features.

• Why it matters: Existing iPSC differentiation can yield motor neurons but often lacks control of rostrocaudal identity and produces heterogeneous HOX profiles, limiting anatomically resolved studies.
• What they did: The authors optimized developmental morphogen combinations and treatment windows to create RiMNs, CiMNs, and LiMNs from iPSC lines from six non-diseased donors balanced by sex, then validated identity by transcriptomic and protein analyses.
• The result: Graded specification from RiMNs through CiMNs to LiMNs matched human week 9 fetal rostrocaudal HOX programs, and multielectrode array plus spike-sorted recordings showed region- and protocol-associated differences in network activity and single-neuron electrophysiology.

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