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Tschuck, J. ; Padmanabhan Nair, V. ; Galhoz, A. ; Zaratiegui, C. ; Tai, H.-M. ; Ciceri, G.* ; Rothenaigner, I. ; Tchieu, J.* ; Stockwell, B.R.* ; Studer, L.* ; Cabianca, D.S. ; Menden, M.P. ; Vincendeau, M. ; Hadian, K.

Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development.

Nat. Commun. 15:7611 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
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The development of functional neurons is a complex orchestration of multiple signaling pathways controlling cell proliferation and differentiation. Because the balance of antioxidants is important for neuronal survival and development, we hypothesized that ferroptosis must be suppressed to gain neurons. We find that removal of antioxidants diminishes neuronal development and laminar organization of cortical organoids, which is fully restored when ferroptosis is inhibited by ferrostatin-1 or when neuronal differentiation occurs in the presence of vitamin A. Furthermore, iron-overload-induced developmental growth defects in C. elegans are ameliorated by vitamin E and A. We determine that all-trans retinoic acid activates the Retinoic Acid Receptor, which orchestrates the expression of anti-ferroptotic genes. In contrast, retinal and retinol show radical-trapping antioxidant activity. Together, our study reveals an unexpected function of vitamin A in coordinating the expression of essential cellular gatekeepers of ferroptosis, and demonstrates that suppression of ferroptosis by radical-trapping antioxidants or by vitamin A is required to obtain mature neurons and proper laminar organization in cortical organoids.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Retinoic Acid; Dopamine Neurons; Derivation; Differentiation; Lineages; Platform
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 15, Issue: 1, Pages: , Article Number: 7611 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Institute of Virology (VIRO)
Institute of Computational Biology (ICB)
Institute of Functional Epigenetics (IFE)
Grants Deutsche Forschungsgemeinschaft
Deutsche Forschungsgemeinschaft (German Research Foundation)