locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity.

The mammalian imprinted locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including (i.e., ) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By profiling cell types at each stage of embryonic stem cell-derived motor neurons (ESC~MNs) that recapitulate spinal cord development, we uncovered that lncRNAs expressed from the locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, and other locus-derived lncRNAs facilitate Ezh2/Jarid2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal genes in postmitotic MNs. Our data thus illustrate that these lncRNAs in the locus, particularly , play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating genes.