Cell Reports
Volume 35, Issue 1, 6 April 2021, 108964
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Article
Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors

https://doi.org/10.1016/j.celrep.2021.108964Get rights and content
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Highlights

  • Arid1a promotes the proliferation-differentiation transition of root progenitors

  • Hh signaling participates in Arid1a’s regulation of tooth root progenitor cell fate

  • Plagl1 endows Arid1a with its cell-type/spatial functional specificity

  • Arid1b is crucial for odontoblast differentiation but not involved in Hh signaling

Summary

Chromatin remodelers often show broad expression patterns in multiple cell types yet can elicit cell-specific effects in development and diseases. Arid1a binds DNA and regulates gene expression during tissue development and homeostasis. However, it is unclear how Arid1a achieves its functional specificity in regulating progenitor cells. Using the tooth root as a model, we show that loss of Arid1a impairs the differentiation-associated cell cycle arrest of tooth root progenitors through Hedgehog (Hh) signaling regulation, leading to shortened roots. Our data suggest that Plagl1, as a co-factor, endows Arid1a with its cell-type/spatial functional specificity. Furthermore, we show that loss of Arid1a leads to increased expression of Arid1b, which is also indispensable for odontoblast differentiation but is not involved in regulation of Hh signaling. This study expands our knowledge of the intricate interactions among chromatin remodelers, transcription factors, and signaling molecules during progenitor cell fate determination and lineage commitment.

Keywords

Arid1a
Plagl1
Hh signaling
cell cycle
stem/progenitor cells

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