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Erythropoietin-driven dynamic proteome adaptations during erythropoiesis prevent iron overload in the developing embryo

Erythropoietin (Epo) ensures survival and proliferation of colony-forming unit erythroid (CFU-E) progenitor cells and their differentiation to hemoglobin-containing mature erythrocytes. A lack of Epo-induced responses causes embryonic lethality, but mechanisms regulating the dynamic communication of...

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Main Authors: Chakraborty, Sajib (Author) , Andrieux, Geoffroy (Author) , Kastl, Philipp (Author) , Adlung, Lorenz (Author) , Altamura, Sandro (Author) , Boehm, Martin E. (Author) , Schwarzmüller, Luisa E. (Author) , Abdullah, Yomn (Author) , Wagner, Marie-Christine (Author) , Helm, Barbara (Author) , Gröne, Hermann-Josef (Author) , Lehmann, Wolf-Dieter (Author) , Börries, Melanie (Author) , Busch, Hauke (Author) , Muckenthaler, Martina (Author) , Schilling, Marcel (Author) , Klingmüller, Ursula (Author)
Format: Article (Journal)
Language:English
Published: September 20, 2022
In: Cell reports
Year: 2022, Volume: 40, Issue: 12, Pages: 1-18
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.111360
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2022.111360
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124722011925
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Author Notes:Sajib Chakraborty, Geoffroy Andrieux, Philipp Kastl, Lorenz Adlung, Sandro Altamura, Martin E. Boehm, Luisa E. Schwarzmüller, Yomn Abdullah, Marie-Christine Wagner, Barbara Helm, Hermann-Josef Gröne, Wolf D. Lehmann, Melanie Boerries, Hauke Busch, Martina U. Muckenthaler, Marcel Schilling, and Ursula Klingmüller
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Summary:Erythropoietin (Epo) ensures survival and proliferation of colony-forming unit erythroid (CFU-E) progenitor cells and their differentiation to hemoglobin-containing mature erythrocytes. A lack of Epo-induced responses causes embryonic lethality, but mechanisms regulating the dynamic communication of cellular alterations to the organismal level remain unresolved. By time-resolved transcriptomics and proteomics, we show that Epo induces in CFU-E cells a gradual transition from proliferation signature proteins to proteins indicative for differentiation, including heme-synthesis enzymes. In the absence of the Epo receptor (EpoR) in embryos, we observe a lack of hemoglobin in CFU-E cells and massive iron overload of the fetal liver pointing to a miscommunication between liver and placenta. A reduction of iron-sulfur cluster-containing proteins involved in oxidative phosphorylation in these embryos leads to a metabolic shift toward glycolysis. This link connecting erythropoiesis with the regulation of iron homeostasis and metabolic reprogramming suggests that balancing these interactions is crucial for protection from iron intoxication and for survival.
Item Description:Das PDF enthält zusätzlich einen Anhang von 8 Seiten
Gesehen am 13.12.2022
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.111360

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