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dc.contributor.authorTátrai, Péter
dc.contributor.authorGergely, Fanni
dc.date.accessioned2022-06-09T14:00:07Z
dc.date.available2022-06-09T14:00:07Z
dc.date.issued2022-07-18
dc.date.submitted2021-05-18
dc.identifier.issn0261-4189
dc.identifier.otherembj2021108739
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337939
dc.description.abstractRed blood cells are produced by terminal erythroid differentiation, which involves the dramatic morphological transformation of erythroblasts into enucleated reticulocytes. Microtubules are important for enucleation, but it is not known if the centrosome, a key microtubule-organizing center, is required as well. Mice lacking the conserved centrosome component, CDK5RAP2, are likely to have defective erythroid differentiation because they develop macrocytic anemia. Here, we show that fetal liver-derived, CDK5RAP2-deficient erythroid progenitors generate fewer and larger reticulocytes, hence recapitulating features of macrocytic anemia. In erythroblasts, but not in embryonic fibroblasts, loss of CDK5RAP2 or pharmacological depletion of centrosomes leads to highly aberrant spindle morphologies. Consistent with such cells exiting mitosis without chromosome segregation, tetraploidy is frequent in late-stage erythroblasts, thereby giving rise to fewer but larger reticulocytes than normal. Our results define a critical role for CDK5RAP2 and centrosomes in spindle formation specifically during blood production. We propose that disruption of centrosome and spindle function could contribute to the emergence of macrocytic anemias, for instance, due to nutritional deficiency or exposure to chemotherapy.
dc.languageen
dc.publisherEMBO
dc.subjectEMBO06
dc.subjectEMBO11
dc.subjectEMBO18
dc.subjectArticle
dc.subjectArticles
dc.subjectblood
dc.subjectcentrosome
dc.subjectenucleation
dc.subjecterythropoiesis
dc.subjectmitotic spindle
dc.titleCentrosome function is critical during terminal erythroid differentiation.
dc.typeArticle
dc.date.updated2022-06-09T14:00:07Z
prism.publicationNameEMBO J
dc.identifier.doi10.17863/CAM.85345
dcterms.dateAccepted2022-05-25
rioxxterms.versionofrecord10.15252/embj.2021108739
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidGergely, Fanni [0000-0002-2441-8095]
dc.identifier.eissn1460-2075
pubs.funder-project-idCancer Research UK (CRUK) (C14303/A17197, C14303/A24455)
cam.issuedOnline2022-06-09


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