Single-nuclei transcriptomic analysis of the subthalamic nucleus reveals different Pitx2-positive subpopulations

The subthalamic nucleus is a compartmentalized structure formed during development with each division serving a different function. A few molecular markers such as transcription factors involved in the formation and maintenance of the STN have been identified, and whilst a few more genes have been reported to be expressed in the STN, the complete transcriptomic landscape of the mature STN remains elusive. So far genes associated with the adult STN have been expressed throughout the structure. It therefore remains to establish if the functional division of this structure is attributed to a molecular diversity comprising of subpopulations. In this study a single-nuclei RNA-sequencing of genetically labelled Pitx2-Cre was conducted to identify the molecular heterogeneity of the STN. The findings revealed two subpopulations of the STN marked by the expression of Baiap3/Fxyd6 or Fgf11. Moreover additional Pitx2 subpopulations with distinct signature markers that characterize neighboring structures of the STN such as the parasubthalamic nucleus, the lateral hypothalamus, the zona incerta and the mammillary nucleus were also identified.