摘要：SummaryRegion-specific neural progenitor cells (NPCs) can be generated from human embryonic stem cells (hESCs) by modulating signaling pathways. However, how intrinsic transcriptional factors contribute to the neural regionalization is not well characterized. Here, we generate region-specific NPCs from hESCs and find that SOX1 is highly expressed in NPCs with the rostral hindbrain identity. Moreover, we find that OTX2 inhibits SOX1 expression, displaying exclusive expression between the two factors. Furthermore,SOX1knockout (KO) leads to the upregulation of midbrain genes and downregulation of rostral hindbrain genes, indicating that SOX1 is required for specification of rostral hindbrain NPCs. Our SOX1 chromatin immunoprecipitation sequencing analysis reveals that SOX1 binds to the distal region ofGBX2to activate its expression. Overexpression ofGBX2largely abrogatesSOX1-KO-induced aberrant gene expression. Taken together, this study uncovers previously unappreciated role of SOX1 in early neural regionalization and provides new information for the precise control of the OTX2/GBX2 interface.Graphical AbstractDisplay OmittedHighlights•SOX1 is highly expressed in rostral hindbrain NPCs derived from hESCs•OTX2 inhibits SOX1 expression in addition to its inhibition on GBX2 expression•SOX1 contributes to the specification of rostral hindbrain NPCs from hESCs•GBX2 is a key factor for SOX1 to function in the rostral hindbrain NPC specificationMolecular Genetics; Developmental Neuroscience
