A 2025 rodent study investigated mechanisms by which erythropoietin (EPO) enables adult neurogenesis and cognitive function:

“We mapped epigenomic and transcriptional landscapes of adult mouse hippocampus under recombinant human EPO (rhEPO) treatment. We discovered significant lineage-specific remodelling of chromatin accessibility predominantly in newly formed pyramidal neurons, highlighting a robust EPO-driven neurogenic response. Notably, transposable elements (TEs), particularly ancient LINEs and SINEs, emerged as critical cis-regulatory elements (cCREs).

EPO is known to be upregulated in the brain under hypoxic or injury conditions, and it has been considered a natural neuroprotective agent. We demonstrated that EPO, a traditionally hematopoietic hormone, can profoundly reprogram the adult neural epigenome to drive neurogenesis.

EPO may activate a specific subclass of dormant regulatory elements to drive nearby genes. Such a mechanism would represent a previously unappreciated mode of gene regulation: the de novo recruitment of ancient genomic elements to drive a contemporary cellular response.

Our data support the model that EPO drives differentiation of progenitors rather than inducing widespread cell division. The net effect is an enrichment of pyramidal neurons at the cost of interneurons. Pyramidal neurons integrate in the hippocampal circuitry, leading to potential implications for mood, memory, cognitive enhancement, and recovery from brain injury.

We propose a conserved evolutionary mechanism at play: ancient TEs embedded in the genome have been repurposed as cCREs in neural cells, and during an EPO-induced neurogenic stimulus, the brain taps into this reservoir of regulatory elements to rapidly reshape gene expression. In evolutionary terms, this represents an efficient strategy.”

https://www.biorxiv.org/content/10.1101/2025.10.13.682070v1.full “Transposable Element-Mediated Epigenomic Remodeling Drives Erythropoietin-Induced Neurogenesis in the Adult Hippocampus”