Human iPSC-Derived Spinal Neural Progenitors Enhance Sensorimotor Recovery in Spinal Cord-Injured NOD-SCID Mice via Differentiation and Microenvironment Regulation

We developed a therapeutic approach by transplanting spinal neural progenitor cells (spNPGs), derived from human induced pluripotent stem cell (iPSC)-generated neuromesodermal progenitors, into a contusive spinal cord injury (SCI) model in NOD-SCID mice. Single-cell RNA sequencing mapped the in vitro differentiation of iPSC-spNPGs, confirming their specification into spinal neuronal lineages. Single-nucleus transcriptomics at one-week post-transplantation showed that the grafted cells differentiated in vivo into motor neurons and two interneuron subtypes (V2 and dI4). Human cord blood monocytes derived iPSC was differentiated into spinal neural progenitor cells with posterior identity. Cells were sampled at distinct time points (day-1, 3, 6, 12 and 18) during the in vitro differentiation process and processed for scRNA-seq libraries construction using Singleron GEXSCOPE® protocol (Singleron Biotechnologies, China). After spNPG tranplation into SCI mice. The nuclei of lesion site in the mouse spinal cord were isolated and performed snRNA-seq using the Chromium platform (10X Genomics, USA).