A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Cell. 2021 Jun 10;184(12):3222-3241.e26. doi: 10.1016/j.cell.2021.04.021. Epub 2021 May 17.


The isocortex and hippocampal formation (HPF) in the mammalian brain play critical roles in perception, cognition, emotion, and learning. We profiled ∼1.3 million cells covering the entire adult mouse isocortex and HPF and derived a transcriptomic cell-type taxonomy revealing a comprehensive repertoire of glutamatergic and GABAergic neuron types. Contrary to the traditional view of HPF as having a simpler cellular organization, we discover a complete set of glutamatergic types in HPF homologous to all major subclasses found in the six-layered isocortex, suggesting that HPF and the isocortex share a common circuit organization. We also identify large-scale continuous and graded variations of cell types along isocortical depth, across the isocortical sheet, and in multiple dimensions in hippocampus and subiculum. Overall, our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation and begins to shed light on its underlying relationship with the development, evolution, connectivity, and function of these two brain structures.

Keywords: GABAergic; cell type; cortex; excitatory neuron; glutamatergic; hippocampus; interneuron; single-cell RNA sequencing; single-cell transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism
  • Glutamic Acid / metabolism
  • Hippocampus / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neocortex / cytology*
  • Transcriptome / genetics*


  • Glutamic Acid