Abstract
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.
Highlights
The regulation of tissue homeostasis is a fundamental function of adult stem cells
Anatomical and molecular identities of mesenchymal stem cells (MSCs) and transit amplifying cells (TACs) in the mouse incisor In order to study the interaction between MSCs and TACs, we first confirmed their in vivo locations using recently published markers
IGF signaling was highly active in TACs, we found that IGF signaling molecules including IGF binding protein (Igfbp3) and the IGF ligand, insulin-like growth factor 2 (Igf2), were all highly enriched in MSCs (Figure 2B)
Summary
The regulation of tissue homeostasis is a fundamental function of adult stem cells. Once stem cells leave their niche, they commit to a more restricted lineage and/or differentiate into specific cell types. In the airway epithelium, the parent epithelial stem cells relay Notch signaling to regulate differentiation in their daughter secretory progenitor cells (Pardo-Saganta et al, 2015). To date, these pioneering studies have exclusively focused on ectodermal organs, and it remains unknown how mesenchymal stem cells (MSCs) interact with TACs to maintain tissue homeostasis. The mechanisms identified in this study could potentially apply to other organs, such as long bone, where MSC and TAC interaction is not well understood but may be crucial for maintaining tissue homeostasis and regeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
