Erythropoietin re-wires cognition-associated transcriptional networks

Manvendra Singh (), Ying Zhao, Vinicius Daguano Gastaldi, Sonja M. Wojcik, Yasmina Curto, Riki Kawaguchi, Ricardo M. Merino, Laura Fernandez Garcia-Agudo, Holger Taschenberger, Nils Brose, Daniel Geschwind, Klaus-Armin Nave and Hannelore Ehrenreich ()
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Manvendra Singh: Max Planck Institute for Multidisciplinary Sciences
Ying Zhao: Max Planck Institute for Multidisciplinary Sciences
Vinicius Daguano Gastaldi: Max Planck Institute for Multidisciplinary Sciences
Sonja M. Wojcik: Max Planck Institute for Multidisciplinary Sciences
Yasmina Curto: Max Planck Institute for Multidisciplinary Sciences
Riki Kawaguchi: University of California Los Angeles
Ricardo M. Merino: Georg-August-University
Laura Fernandez Garcia-Agudo: Max Planck Institute for Multidisciplinary Sciences
Holger Taschenberger: Max Planck Institute for Multidisciplinary Sciences
Nils Brose: Max Planck Institute for Multidisciplinary Sciences
Daniel Geschwind: University of California Los Angeles
Klaus-Armin Nave: Max Planck Institute for Multidisciplinary Sciences
Hannelore Ehrenreich: Max Planck Institute for Multidisciplinary Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Recombinant human erythropoietin (rhEPO) has potent procognitive effects, likely hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO remained obscure. Here, we provide transcriptional hippocampal profiling of male mice treated with rhEPO. Based on ~108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures. By temporal profiling and gene regulatory analysis, we build developmental trajectory of CA1 pyramidal neurons derived from multiple predecessor lineages and elucidate gene regulatory networks underlying their fate determination. With EPO as ‘tool’, we discover populations of newly differentiating pyramidal neurons, overpopulating to ~200% upon rhEPO with upregulation of genes crucial for neurodifferentiation, dendrite growth, synaptogenesis, memory formation, and cognition. Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40332-8

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DOI: 10.1038/s41467-023-40332-8

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