Journal
DEVELOPMENT
Volume 148, Issue 8, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.198838
Keywords
Arid1a; Mesenchymal stem cells; Transit-amplifying cells; Cell cycle; Mitosis
Categories
Funding
- National Institute of Dental and Craniofacial Research, National Institutes of Health [R01 DE025221, R01 DE022503, U01 DE028729, R01 DE012711]
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The research reveals that Arid1a maintains tissue homeostasis by inhibiting the Aurka-Cdk1 axis, limiting proliferation of TACs, and promoting their differentiation, while loss of Arid1a leads to reduction of the MSC population.
Stem cells self-renew or give rise to transit-amplifying cells (TACs) that differentiate into specific functional cell types. The fate determination of stem cells to TACs and their transition to fully differentiated progeny is precisely regulated to maintain tissue homeostasis. Arid1a, a core component of the switch/sucrose nonfermentable complex, performs epigenetic regulation of stage- and tissue-specific genes that is indispensable for stem cell homeostasis and differentiation. However, the functional mechanism of Arid1a in the fate commitment of mesenchymal stem cells (MSCs) and their progeny is not clear. Using the continuously growing adult mouse incisor model, we show that Arid1a maintains tissue homeostasis through limiting proliferation, promoting cell cycle exit and differentiation of TACs by inhibiting the Aurka-Cdk1 axis. Loss of Arid1a overactivates the Aurka-Cdk1 axis, leading to expansion of the mitotic TAC population but compromising their differentiation ability. Furthermore, the defective homeostasis after loss of Arid1a ultimately leads to reduction of the MSC population. These findings reveal the functional significance of Arid1a in regulating the fate of TACs and their interaction with MSCs to maintain tissue homeostasis.
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