The role of specialized cell cycles during erythroid lineage development: insights from single-cell RNA sequencing
UMass Chan AffiliationsMolecular, Cell and Cancer Biology
Document TypeJournal Article
Erythropoietic stress response
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AbstractEarly 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.
SourceSocolovsky 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.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51174
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