摘要Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the host microenvironment,which in turn affects the functionality of transplanted human neural stem/progenitor cells and potentially limits their benefits for neurorepair.However,the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood.Here,we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment.Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3.ID3-depleted human neural stem/progenitor cells,generated by CRISPR/Cas9-mediated genome editing,reduced astrocyte formation in response to astrogenic stimuli.Instead,ID3-depleted human neural stem/progenitor cells had a bipolar,immature glial progenitor cell phenotype.These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth.We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells,potentially enhancing their capacity to promote central nervous system repair.