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An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

ABSTRACT: An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

PROVIDER: PRJNA1048338 | ENA |

REPOSITORIES: ENA

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An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

Project description:An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

| PRJNA1048336 | ENA

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

Project description:An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

| PRJNA1048337 | ENA

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

Project description:An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

| PRJNA1048327 | ENA

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

Project description:An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

| PRJNA1048335 | ENA

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

Project description:An unsolved mystery in biology is how human-specific traits were acquired during evolution. Here, we report that an evolutionary ancient non-coding element—human accelerated region 123 (HAR123)—has undergone rapid evolution specifically in the human lineage and confers human-specific functions. HAR123 is a neural enhancer that promotes the generation of human neuroectoderm and neural progenitor cells by upregulating the transcriptional repressor HIC1. The human and chimpanzee versions of HAR123 exhibit different properties, consistent with HAR123 being selected for new functions since the human-chimpanzee split. To address the in vivo functions of HAR123, we generated HAR123-knockout mice, which exhibit a specific defect in “re-learning.” Together, our study supports a model in which HAR123 has rapidly evolved in the human lineage to influence neural generation and, ultimately, cognitive flexibility.

2025-07-15 | GSE249251 | GEO

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

2025-07-15 | GSE249250 | GEO

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

2025-07-15 | GSE249249 | GEO

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

2025-07-15 | GSE249252 | GEO

An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-07-15 | GSE249253 | GEO

Human CLOCK enhances cognitive flexibility by altering cortical excitatory neuron function

Project description:A BAC containing human CLOCK gene with flanking regulatory region was transferred to mice. The humazied (HU) mice outperformed wildtype (WT) in a reversal learning task, and hence suggested enhanced cognitive flexibility in HU mice. IHC of frontal cortex suggested that the enhanced cognitive flexibility in HU mice might result from the increased neuronal density, dendritic arborization, and spine density. In order to determine the molecular mechanism, we conducted single-nuclei RNA-seq on frontal cortex from postnatal 7 day (P7) and P56 mice. In the excitatory neuron, genes that upregulated in HU mice were enriched for dendritic growth (e.g. Tenm2 and Flrt2), spine formation (e.g. Cntn5 and Sorcs2), and energy metabolism (e.g. Suclg1 and Cox8a).

2025-04-18 | GSE224759 | GEO

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