This study presents a comprehensive single-cell transcriptomic analysis of the human brain, focusing on both adult and fetal tissues. The researchers used single-cell RNA sequencing to capture the cellular complexity of the human brain at a whole transcriptome level. They obtained brain tissue from patients undergoing temporal lobectomy for medically refractory seizures and mesial temporal sclerosis (MTS), as well as from prenatal brain samples at 16-18 weeks post-gestation. The analysis identified all major neuronal, glial, and vascular cell types, including subtypes of interneurons, and revealed the expression patterns of genes typically used to classify these cells. The study also compared gene expression profiles between fetal and adult neurons, identifying gradients of expression between quiescent and replicating fetal neurons. Additionally, the researchers observed the expression of major histocompatibility complex type I (MHCi) genes in a subset of adult neurons, which was not detected in fetal neurons. This work demonstrates the utility of single-cell RNA sequencing in studying the adult human brain and lays the foundation for a comprehensive cellular atlas of the human brain.This study presents a comprehensive single-cell transcriptomic analysis of the human brain, focusing on both adult and fetal tissues. The researchers used single-cell RNA sequencing to capture the cellular complexity of the human brain at a whole transcriptome level. They obtained brain tissue from patients undergoing temporal lobectomy for medically refractory seizures and mesial temporal sclerosis (MTS), as well as from prenatal brain samples at 16-18 weeks post-gestation. The analysis identified all major neuronal, glial, and vascular cell types, including subtypes of interneurons, and revealed the expression patterns of genes typically used to classify these cells. The study also compared gene expression profiles between fetal and adult neurons, identifying gradients of expression between quiescent and replicating fetal neurons. Additionally, the researchers observed the expression of major histocompatibility complex type I (MHCi) genes in a subset of adult neurons, which was not detected in fetal neurons. This work demonstrates the utility of single-cell RNA sequencing in studying the adult human brain and lays the foundation for a comprehensive cellular atlas of the human brain.