Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Chengdu, China
Jifan Feng
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Jingyuan Li
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Hu Zhao
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Jinzhi He
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Chengdu, China
Yuan Yuan
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Tingwei Guo
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Jiahui Du
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Mark Urata
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, United States
Interaction between adult stem cells and their progeny is critical for tissue homeostasis and regeneration. In multiple organs, mesenchymal stem cells (MSCs) give rise to transit amplifying cells (TACs), which then differentiate into different cell types. However, whether and how MSCs interact with TACs remains unknown. Using the adult mouse incisor as a model, we present in vivo evidence that TACs and MSCs have distinct genetic programs and engage in reciprocal signaling cross talk to maintain tissue homeostasis. Specifically, an IGF-WNT signaling cascade is involved in the feedforward from MSCs to TACs. TACs are regulated by tissue-autonomous canonical WNT signaling and can feedback to MSCs and regulate MSC maintenance via Wnt5a/Ror2-mediated non-canonical WNT signaling. Collectively, these findings highlight the importance of coordinated bidirectional signaling interaction between MSCs and TACs in instructing mesenchymal tissue homeostasis, and the mechanisms identified here have important implications for MSC–TAC interaction in other organs.
