Spatial patterning of transcriptional and regulatory programs in the primate subcortex

bioRxiv (Cold Spring Harbor Laboratory) 2025

Shu Dan, Meghan A. Turner, Michael DeBerardine, Lakme Caceres, Victor E. Nieto-Caballero, Jessica Schembri, Kirsten Levandowski, Christopher Cardenas et al.

Abstract

Abstract Mammalian brain cell identity is shaped by intrinsic factors and external context. We present a spatially resolved transcriptomic and gene regulatory atlas of cell types found across all subcortical brain regions in a primate - the marmoset monkey. Dense sampling and cross-species integrations revealed spatially precise neuronal assemblies, including in complex structures such as hypothalamus. We find chromatin accessibility and transcriptional identity are spatially tuned within and across subcortical structures. Spatial gradients within subfields of the hippocampal formation are predominantly orchestrated by graded transcription factors coupled with graded enhancers. The primate-expanded population of GABAergic neurons in the thalamus shares transcriptional and regulatory syntax with neurons in superior colliculus, reflecting an evolutionary adaptation compared with rodents. We show that unexpected transcriptional convergence, such as between striatal GABAergic medium spiny neurons and telencephalic glutamatergic neurons, can arise when distinct gene regulatory networks impinge on the same downstream genes.

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