Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors
Jiahui Du,
Junjun Jing,
Yuan Yuan,
Jifan Feng,
Xia Han,
Shuo Chen,
Xiang Li,
Weiqun Peng,
Jian Xu,
Thach-Vu Ho,
Xinquan Jiang,
Yang Chai
Affiliations
Jiahui Du
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA; Department of Prosthodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Junjun Jing
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Yuan Yuan
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Jifan Feng
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Xia Han
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Shuo Chen
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Xiang Li
Department of Physics, George Washington University, Washington, DC 20052, USA
Weiqun Peng
Department of Physics, George Washington University, Washington, DC 20052, USA
Jian Xu
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Thach-Vu Ho
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Xinquan Jiang
Department of Prosthodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Yang Chai
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
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.
