Single-cell characterization of human periodontal ligament (PDL) cells reveals uniformly mesenchymal populations in matched maxilla and mandible pairs from four donors
- 1Helmholtz-Institute for Biomedical Engineering, Biointerface Laboratory and Medical Faculty, RWTH Aachen University Hospital, Aachen, Germany
Abstract
The periodontal ligament (PDL) is a mechanically active connective tissue whose fibroblasts and resident progenitor cells drive tooth support, remodeling, and regeneration. Although PDL cell populations are known to be heterogeneous, the composition of expanded primary PDL cultures and the extent to which anatomical origin shapes their transcriptome remain incompletely defined. Here we applied single-cell RNA sequencing to cultured primary PDL cells isolated from matched upper (maxilla) and lower (mandible) jaw sites of four donors, yielding 43,423 cells that were integrated across donors and analyzed by unsupervised clustering. The expanded cultures were uniformly mesenchymal and fibroblastic, essentially devoid of endothelial and immune signatures, and resolved into ten functionally distinct fibroblast substates rather than discrete cell types, including proliferating, collagen- and extracellular-matrix-high, contractile, and progenitor-like populations. Donor identity was the dominant source of transcriptional variation, with several substates restricted to individual donors. A donor-controlled comparison of maxilla versus mandible revealed only a small set of differentially expressed genes, headed by craniofacial positional-identity transcription factors (PITX1 higher in the mandible; BARX1, ALX1, and NKX6-1 higher in the maxilla), indicating that cultured PDL cells retain embryonic positional memory. In contrast, curated wound-healing gene modules did not differ significantly between jaws, and the transcriptional data therefore did not support the clinical impression of faster healing in the maxilla, suggesting that the healing asymmetry more likely reflects vascular, mechanical, and inflammatory signaling factors acting beyond the steady-state transcriptome. These findings characterize the cellular composition of expanded PDL cultures and identify positional identity as the principal jaw-dependent transcriptional feature.
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BibTeX
@misc{radermacher2026singlecell,
title = {{Single-cell characterization of human periodontal ligament (PDL) cells reveals uniformly mesenchymal populations in matched maxilla and mandible pairs from four donors}},
author = {C. Radermacher and R. Dzhanaev and C. Hasberg and S. Neuss-Stein and A. Gorgels and J. Moellmann and N. Marx and A. Babler and C. Kuppe and R. Bastos-Craveiro and M. Wolf and A. Modabber and W. Jahnen-Dechent and I. Knaup},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749128},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749128v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Single-cell characterization of human periodontal ligament (PDL) cells reveals uniformly mesenchymal populations in matched maxilla and mandible pairs from four donors
AU - C. Radermacher
AU - R. Dzhanaev
AU - C. Hasberg
AU - S. Neuss-Stein
AU - A. Gorgels
AU - J. Moellmann
AU - N. Marx
AU - A. Babler
AU - C. Kuppe
AU - R. Bastos-Craveiro
AU - M. Wolf
AU - A. Modabber
AU - W. Jahnen-Dechent
AU - I. Knaup
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749128
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749128v1
AB - The periodontal ligament (PDL) is a mechanically active connective tissue whose fibroblasts and resident progenitor cells drive tooth support, remodeling, and regeneration. Although PDL cell populations are known to be heterogeneous, the composition of expanded primary PDL cultures and the extent to which anatomical origin shapes their transcriptome remain incompletely defined. Here we applied single-cell RNA sequencing to cultured primary PDL cells isolated from matched upper (maxilla) and lower (mandible) jaw sites of four donors, yielding 43,423 cells that were integrated across donors and analyzed by unsupervised clustering. The expanded cultures were uniformly mesenchymal and fibroblastic, essentially devoid of endothelial and immune signatures, and resolved into ten functionally distinct fibroblast substates rather than discrete cell types, including proliferating, collagen- and extracellular-matrix-high, contractile, and progenitor-like populations. Donor identity was the dominant source of transcriptional variation, with several substates restricted to individual donors. A donor-controlled comparison of maxilla versus mandible revealed only a small set of differentially expressed genes, headed by craniofacial positional-identity transcription factors (PITX1 higher in the mandible; BARX1, ALX1, and NKX6-1 higher in the maxilla), indicating that cultured PDL cells retain embryonic positional memory. In contrast, curated wound-healing gene modules did not differ significantly between jaws, and the transcriptional data therefore did not support the clinical impression of faster healing in the maxilla, suggesting that the healing asymmetry more likely reflects vascular, mechanical, and inflammatory signaling factors acting beyond the steady-state transcriptome. These findings characterize the cellular composition of expanded PDL cultures and identify positional identity as the principal jaw-dependent transcriptional feature.
ER -