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SOX1 is required for the specification of rostral hindbrain neural progenitor cells from human embryonic stem cells

ABSTRACT: Region-specific neural progenitor cells (NPCs) can be generated from human embryonic stem cells (hESCs) through modulating signaling pathways. However, how intrinsic transcriptional factors contribute to the neural regionalization are 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, SOX1 knockout (KO) leads to up-regulation of midbrain genes and down-regulation of rostral hindbrain genes, indicating that SOX1 is necessary for specification of rostral hindbrain NPCs. Our SOX1 ChIP-sequencing analysis reveals that SOX1 binds to the distal region of GBX2 to activate its expression. Overexpression of GBX2 largely abrogates SOX1-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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138218 | GEO | 2020/08/26

REPOSITORIES: GEO

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