Erythropoietin re-wires cognition-associated transcriptional networks

2023 | journal article. A publication with affiliation to the University of Göttingen.

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​Erythropoietin re-wires cognition-associated transcriptional networks​
Singh, M.; Zhao, Y.; Gastaldi, V. D.; Wojcik, S. M.; Curto, Y.; Kawaguchi, R. & Merino, R. M. et al.​ (2023) 
Nature Communications14(1).​ DOI: https://doi.org/10.1038/s41467-023-40332-8 

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Authors
Singh, Manvendra; Zhao, Ying; Gastaldi, Vinicius Daguano; Wojcik, Sonja M.; Curto, Yasmina; Kawaguchi, Riki; Merino, Ricardo M.; Garcia-Agudo, Laura Fernandez; Taschenberger, Holger; Brose, Nils; Ehrenreich, Hannelore
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.
Issue Date
2023
Journal
Nature Communications 
Project
TRR 274: Checkpoints of Central Nervous System Recovery 
TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease 
Working Group
RG Ehrenreich (Clinical Neuroscience) 
RG Nave (Neurogenetics) 
External URL
https://rdp.sfb274.de/literature/publications/142
eISSN
2041-1723
Language
English

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