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A chemical screening approach to identify novel key mediators of erythroid enucleation

Wölwer, Christina B., Pase, Luke B., Pearson, Helen B., Gödde, Nathan J., Lackovic, Kurt, Huang, David C. S., Russell, Sarah M. and Humbert, Patrick O. 2015. A chemical screening approach to identify novel key mediators of erythroid enucleation. PLoS ONE 10 (11) , e0142655. 10.1371/journal.pone.0142655

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Abstract

Erythroid enucleation is critical for terminal differentiation of red blood cells, and involves extrusion of the nucleus by orthochromatic erythroblasts to produce reticulocytes. Due to the difficulty of synchronizing erythroblasts, the molecular mechanisms underlying the enucleation process remain poorly understood. To elucidate the cellular program governing enucleation, we utilized a novel chemical screening approach whereby orthochromatic cells primed for enucleation were enriched ex vivo and subjected to a functional drug screen using a 324 compound library consisting of structurally diverse, medicinally active and cell permeable drugs. Using this approach, we have confirmed the role of HDACs, proteasomal regulators and MAPK in erythroid enucleation and introduce a new role for Cyclin-dependent kinases, in particular CDK9, in this process. Importantly, we demonstrate that when coupled with imaging analysis, this approach provides a powerful means to identify and characterize rate limiting steps involved in the erythroid enucleation process.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 15 August 2017
Date of Acceptance: 26 October 2015
Last Modified: 03 Apr 2019 11:37
URI: http://orca-mwe.cf.ac.uk/id/eprint/103601

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