Runx2+ Niche Cells Maintain Incisor Mesenchymal Tissue Homeostasis through IGF Signaling

Cell Reports

Junjun Jing¹  Chelsea Lee²  Xia Han²  Jifan Feng²  Thach-Vu Ho²  Quan Wen²  Yuan Yuan²  Shuo Chen²  Yang Chai³ 

[1] Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China;Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA;Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA;

关键词: Runx2;    mesenchymal stem cells;    niche;    transit-amplifying cells;    adult mouse incisor;    IGF signaling;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown