Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Journal Club
  • Published:

Development

Changes in cell-cycle rate drive diverging cell fates

Nature Reviews Genetics (2024)Cite this article

Subjects

Changes in the concentrations of transcription factors drive cells to commit to different fates. These concentration changes can be achieved through mechanisms such as transcriptional activation or protein degradation. However, the role of the cell cycle in regulating transcription factor levels and cell fate remains underappreciated. During differentiation, cells often divide before committing to divergent fates, enabling the generation of new cells and maintenance of a self-renewing progenitor population. Differences in the proliferation rate of these populations emerge as their fates diverge. Thus, it remains challenging to separate the role of the cell cycle in establishing cell identity from cell identity itself.

In 2013, to address how cell cycle influences the divergence of myeloid and lymphoid cells from a progenitor population, Kueh et al. examined how expression of the pioneer transcription factor PU.1 generated distinct cell fates in mice. At high levels, PU.1 positively regulates its own transcription to maintain myeloid identity in macrophages. Simultaneously, PU.1 reduces the cycling rate of myeloid cells. Increased transcription of Spi1, the gene encoding PU.1, might drive accumulation of PU.1 in progenitors, reinforcing expression and commitment to the myeloid fate. Alternatively, lengthening of the cell cycle may enable PU.1 to accumulate and drive commitment. To examine these competing models of cell-fate regulation, Kueh et al. established a transgenic mouse model with a bicistronic cassette including a fluorescent marker, PU.1–GFP. As PU.1–GFP levels mirror expression of endogenous PU.1, the rate of PU.1 synthesis can be monitored as cells transition from progenitors into B cells and macrophages.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

Original article

Related article

  • Babos, K. N. et al. Mitigating antagonism between transcription and proliferation allows near-deterministic cellular reprogramming. Cell Stem Cell 25, 486–500 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Kate E. Galloway

Authors
  1. Kate E. Galloway
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kate E. Galloway.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Galloway, K.E. Changes in cell-cycle rate drive diverging cell fates. Nat Rev Genet (2024). https://doi.org/10.1038/s41576-024-00714-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/s41576-024-00714-0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing