Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, 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
Quan Wen
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
Chelsea Lee
Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA
Yang Chai
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Summary: Stem cell niches provide a microenvironment to support the self-renewal and multi-lineage differentiation of stem cells. Cell-cell interactions within the niche are essential for maintaining tissue homeostasis. However, the niche cells supporting mesenchymal stem cells (MSCs) are largely unknown. Using single-cell RNA sequencing, we show heterogeneity among Gli1+ MSCs and identify a subpopulation of Runx2+/Gli1+ cells in the adult mouse incisor. These Runx2+/Gli1+ cells are strategically located between MSCs and transit-amplifying cells (TACs). They are not stem cells but help to maintain the MSC niche via IGF signaling to regulate TAC proliferation, differentiation, and incisor growth rate. ATAC-seq and chromatin immunoprecipitation reveal that Runx2 directly binds to Igfbp3 in niche cells. This Runx2-mediated IGF signaling is crucial for regulating the MSC niche and maintaining tissue homeostasis to support continuous growth of the adult mouse incisor, providing a model for analysis of the molecular regulation of the MSC niche.
