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    The role of specialized cell cycles during erythroid lineage development: insights from single-cell RNA sequencing

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    Authors
    Socolovsky, Merav
    UMass Chan Affiliations
    Molecular, Cell and Cancer Biology
    Document Type
    Journal Article
    Publication Date
    2022-06-27
    Keywords
    CDK inhibitors
    Cell cycle
    Erythropoiesis
    Erythropoietic stress response
    Glucocorticoids
    Replication forks
    
    Metadata
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    Link to Full Text
    https://doi.org/10.1007/s12185-022-03406-9
    Abstract
    Early erythroid progenitors known as CFU-e undergo multiple self-renewal cell cycles. The CFU-e developmental stage ends with the onset of erythroid terminal differentiation (ETD). The transition from CFU-e to ETD is a critical cell fate decision that determines erythropoietic rate. Here we review recent insights into the regulation of this transition, garnered from flow cytometric and single-cell RNA sequencing studies. We find that the CFU-e/ETD transition is a rapid S phase-dependent transcriptional switch. It takes place during an S phase that is much shorter than in preceding or subsequent cycles, as a result of globally faster replication forks. Furthermore, it is preceded by cycles in which G1 becomes gradually shorter. These dramatic cell cycle and S phase remodeling events are directly linked to regulation of the CFU-e/ETD switch. Moreover, regulators of erythropoietic rate exert their effects by modulating cell cycle duration and S phase speed. Glucocorticoids increase erythropoietic rate by inducing the CDK inhibitor p57KIP2, which slows replication forks, inhibiting the CFU-e/ETD switch. Conversely, erythropoietin promotes induction of ETD by shortening the cycle. S phase shortening was reported during cell fate decisions in non-erythroid lineages, suggesting a fundamentally new developmental role for cell cycle speed.
    Source
    Socolovsky M. The role of specialized cell cycles during erythroid lineage development: insights from single-cell RNA sequencing. Int J Hematol. 2022 Aug;116(2):163-173. doi: 10.1007/s12185-022-03406-9. Epub 2022 Jun 27. PMID: 35759181.
    DOI
    10.1007/s12185-022-03406-9
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/51174
    PubMed ID
    35759181
    Rights
    © 2022. Japanese Society of Hematology.
    ae974a485f413a2113503eed53cd6c53
    10.1007/s12185-022-03406-9
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