Spatial multi-omics of mouse incisor mesenchyme reveals metabolic remodeling during the MSC-to-TAC transition
4 affiliations
- 1College of Life Sciences, Nankai University, Tianjin, China
- 2Chinese Institute for Brain Research (CIBR), Beijing, China
- 3Clinical Research Center for Oral Tissue Deficiency Diseases of Fujian Province & Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fujian, China
- 4College of Stomatology, Qujing University of Medicine & Health Sciences, Qujing, China
Abstract
The continuously growing mouse incisor provides a useful model for investigating stem cell niche organization and the MSC-to-TAC transition because it contains spatially distinct mesenchymal stem/stromal cell (MSC)-enriched and transit-amplifying cell (TAC)-enriched compartments and abundant TAC populations. However, the metabolic programs associated with MSCs and their transition to TACs within the native tissue environment remain poorly understood. Here, we integrated region-resolved transcriptomics, proteomics, and metabolomics with single-cell RNA sequencing to characterize metabolic remodeling associated with the MSC-to-TAC transition in the mouse incisor pulp. We found that the MSC-enriched apical pulp was enriched for molecular features associated with fatty acid β-oxidation and ketone body metabolism, whereas the TAC-enriched mitotic pulp showed molecular signatures associated with the tricarboxylic acid cycle, oxidative phosphorylation, and nucleotide biosynthesis. Integrated transcriptomic and proteomic analyses revealed lower mRNA-protein concordance in the MSC-enriched apical pulp, consistent with a contribution of post-transcriptional regulation, whereas the TAC-enriched mitotic pulp showed tighter mRNA-protein coupling. Metabolite profiling further showed higher abundance of acyl-carnitines and ketone bodies in the MSC-enriched apical pulp and higher abundance of glutamine, aspartate, and purine intermediates in the TAC-enriched mitotic pulp. Pseudotime analysis suggested coordinated changes in transcriptional programs related to fatty acid oxidation, mitochondrial oxidative metabolism, and nucleotide synthesis along an MSC-to-TAC trajectory. Collectively, our study establishes a region-resolved multi-omics atlas of metabolic remodeling associated with the MSC-to-TAC transition in the mouse incisor and provides insights into the metabolic features associated with stem cell activation, progenitor expansion, and tissue homeostasis in the native dental stem cell niche.
Related
- Single-cell and spatial transcriptomics in intrahepatic cholangiocarcinoma: spatial immune ecosystems, metabolic remodeling, and immunotherapeutic implications
- Lactylation-mediated remodeling of spatial immunometabolic niches in lung cancer: metabolic origins, cellular interactions, and molecular mechanisms
- An epithelial–mesenchymal transition-like synovial stromal-remodeling programme associated with knee osteoarthritis pain: Exploratory transcriptomic discovery and spatial analysis
- Spatial Remodeling of the Immune Microenvironment During Laryngeal Carcinogenesis Reveals Prognostic Immune Patterns in Laryngeal Squamous Cell Carcinoma
- SPEAR: Spatial Epitranscriptomic Analysis by Mass Spectrometry Reveals Localized RNA Modification Remodeling During Glioma Progression
BibTeX
@article{wang2026spatial,
title = {{Spatial multi-omics of mouse incisor mesenchyme reveals metabolic remodeling during the MSC-to-TAC transition}},
author = {Yuling Wang and Zexi Chen and Tingting Chen and Yue Zhao and Xiaoqian Yu and Qian Li and Xinshuang Zhang and Zhanying Bi and Meng Ye and Fengzhi Li and Xiangyu Zhou and Zhen Li and Li Zhang and Woo-pimg Ge and Wange Lv and Hongji Pu and Hu Zhao},
journal = {International Journal of Oral Science},
year = {2026},
month = oct,
doi = {10.1038/s41368-026-00469-w},
url = {https://doi.org/10.1038/s41368-026-00469-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Spatial multi-omics of mouse incisor mesenchyme reveals metabolic remodeling during the MSC-to-TAC transition
AU - Yuling Wang
AU - Zexi Chen
AU - Tingting Chen
AU - Yue Zhao
AU - Xiaoqian Yu
AU - Qian Li
AU - Xinshuang Zhang
AU - Zhanying Bi
AU - Meng Ye
AU - Fengzhi Li
AU - Xiangyu Zhou
AU - Zhen Li
AU - Li Zhang
AU - Woo-pimg Ge
AU - Wange Lv
AU - Hongji Pu
AU - Hu Zhao
PY - 2026
DA - 2026/10/31
JO - International Journal of Oral Science
DO - 10.1038/s41368-026-00469-w
UR - https://doi.org/10.1038/s41368-026-00469-w
AB - The continuously growing mouse incisor provides a useful model for investigating stem cell niche organization and the MSC-to-TAC transition because it contains spatially distinct mesenchymal stem/stromal cell (MSC)-enriched and transit-amplifying cell (TAC)-enriched compartments and abundant TAC populations. However, the metabolic programs associated with MSCs and their transition to TACs within the native tissue environment remain poorly understood. Here, we integrated region-resolved transcriptomics, proteomics, and metabolomics with single-cell RNA sequencing to characterize metabolic remodeling associated with the MSC-to-TAC transition in the mouse incisor pulp. We found that the MSC-enriched apical pulp was enriched for molecular features associated with fatty acid β-oxidation and ketone body metabolism, whereas the TAC-enriched mitotic pulp showed molecular signatures associated with the tricarboxylic acid cycle, oxidative phosphorylation, and nucleotide biosynthesis. Integrated transcriptomic and proteomic analyses revealed lower mRNA-protein concordance in the MSC-enriched apical pulp, consistent with a contribution of post-transcriptional regulation, whereas the TAC-enriched mitotic pulp showed tighter mRNA-protein coupling. Metabolite profiling further showed higher abundance of acyl-carnitines and ketone bodies in the MSC-enriched apical pulp and higher abundance of glutamine, aspartate, and purine intermediates in the TAC-enriched mitotic pulp. Pseudotime analysis suggested coordinated changes in transcriptional programs related to fatty acid oxidation, mitochondrial oxidative metabolism, and nucleotide synthesis along an MSC-to-TAC trajectory. Collectively, our study establishes a region-resolved multi-omics atlas of metabolic remodeling associated with the MSC-to-TAC transition in the mouse incisor and provides insights into the metabolic features associated with stem cell activation, progenitor expansion, and tissue homeostasis in the native dental stem cell niche.
SN - 1674-2818
SN - 2049-3169
ER -