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Reciprocal interaction between mesenchymal stem cells and transit amplifying cells regulates tissue homeostasis

Research output: Contribution to journalArticlepeer-review

Junjun Jing, Jifan Feng, Jingyuan Li, Hu Zhao, Thach Vu Ho, Jinzhi He, Yuan Yuan, Tingwei Guo, Jiahui Du, Mark Urata, Paul Sharpe, Yang Chai

Original languageEnglish
Article numbere59459
Pages (from-to)1-18
Number of pages18
PublishedJan 2021

Bibliographical note

Funding Information: We thank Julie Mayo and Bridget Samuels for critical reading of the manuscript. We acknowledge USC Libraries Bioinformatics Service for assisting with data analysis. The bioinformatics software and computing resources used in the analysis are funded by the USC Office of Research and the Norris Medical Library. This study was supported by grants from the National Institute of Dental and Craniofacial Research and National Institutes of Health (R01 DE025221 and R01 DE012711). Publisher Copyright: © Jing et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


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.

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