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Data from: Delineating the early transcriptional specification of the mammalian trachea and esophagus

Kuwahara, Akela1; Bush, Jeffrey1

Published May 11, 2020; Updated Dec 29, 2020 on Dryad. https://doi.org/10.7272/Q6WW7FVB

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Abstract

The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2.1 and SOX2 are hypothesized to be co-repressive master regulators of tracheal and esophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By combining single cell RNA-sequencing with bulk RNA-sequencing of Nkx2.1 mutants and NKX2.1 ChIP-sequencing in mouse embryos, we delineate the NKX2.1 transcriptional program in trachea and esophagus specification, and reveal a previously unknown NKX2.1-independent transcriptional program. To decouple regulation of the NKX2.1 transcriptional program from regulation by SOX2, we interrogate the expression of our newly-identified tracheal and esophageal markers in Sox2/Nkx2.1 compound mutants. Finally, we discover that NKX2.1 binds directly to Shh and Wnt7b and regulates their expression to control mesenchymal specification to cartilage and smooth muscle, coupling epithelial identity with mesenchymal specification. Together, these data create a new framework for understanding early tracheal and esophageal fate specification at the genome-wide level.