摘要：SummaryRobust axon regeneration of motoneurons (MNs) occurs in rodent models upon peripheral nerve injury (PNI). However, genome-wide dynamic molecules and permissive microenvironment following insult in MNs remain largely unknown. Here, we firstly tackled by high-coverage and massive sequencing of laser-dissected individual ChAT+cells to uncover molecules and pro-regenerative programs of MNs from injury to the regenerating phase after PNI. “Injured” populations at 1d∼7d were well distinguished and three response phases were well defined by elucidating with several clues (Gap43, etc). We found remarkable changes of genes expressed by injured motoneurons to activate and enhance intrinsic axon regrowth or crosstalk with other cellular or non-cellular counterpart in the activated regenerative microenvironment, specifically microglia/macrophage. We also identified an injury and regeneration-associated module and critical regulators including core transcription factors (Atf3,Arid5a,Klf6,Klf7,Jun,Stat3, andMyc). This study provides a vital resource and critical molecules for studying neural repair of axotomized motoneurons.Graphical abstractDisplay OmittedHighlights•Transcriptional landscape of motoneurons (MNs) and its niches upon axonal injury•High dynamic niches and cell heterogeneity around injured and the regenerating MNs•Screen critical master regulators that may initiate regeneration program in MNs•Knockdown of Arid5a significantly reduces neurite outgrowthin vitroMolecular physiology; Neuroscience; Omics
