Spatial multi-omics of mouse incisor mesenchyme reveals metabolic remodeling during the MSC-to-TAC transition.

Authors

Yuling Wang, Zexi Chen, Tingting Chen, Yue Zhao, Xiaoqian Yu, Qian Li, Xinshuang Zhang, Zhanying Bi, Meng Ye, Fengzhi Li, Xiangyu Zhou, Zhen Li, Li Zhang, Woo-Pimg Ge, Wange Lv, Hongji Pu, Hu Zhao

Published in

International journal of oral science. Volume 18. Issue 1. Oct 31, 2026. Epub Oct 31, 2026.

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.

PMID:
42966754
Bibliographic data and abstract were imported from PubMed on 01 Nov 2026.

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