Biology subjects

Radermacher, C.

Publications and source records attributed to Radermacher, C..

3 recordsLinked to original sources

bioRxiv2026

Single-cell characterization of human periodontal ligament (PDL) cells reveals uniformly mesenchymal populations in matched maxilla and mandible pairs from four donors

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.

genomics↗

bioRxiv2026

Oncodevelopmental plasticity of the skeleton in myeloid neoplasms

Myelofibrosis in patients with myeloproliferative neoplasms (MPNs) is traditionally characterized by bone marrow fibrosis and osteosclerosis, with de novo bone formation commonly attributed to impaired osteoclast-mediated resorption. Here, we challenge this paradigm by demonstrating that a solitary clonal driver mutation simultaneously induces pathological bone formation and resorption, with osteosclerosis acting to conceal localized and active bone destruction rather than inhibiting it. Through population analysis; clinical imaging; patient-derived multi-tissue sequencing; murine models and organ-on-a-chip systems, we demonstrate that spatial and ontogeny-dependent remodeling in mesoderm- and neural crest-derived bones is mechanistically interconnected via a previously unidentified osteochondral stromal injury program. Neural crest-derived stromal cells suppress osteogenic programs and undergo injury-induced lineage plasticity with ectopic chondrogenesis, mirroring pathological remodeling in mesoderm-derived growth plate regions. This shared injury response promotes osteoclastogenesis and is mediated by a conserved Thrombospondin 1+ (THBS1+) stromal population that links fibrotic remodeling to bone loss. Combined pharmacological inhibition of THBS1 and JAK signaling reduces myeloproliferation, halts fibrosis progression, and restores two developmentally distinct bones, establishing THBS1 as a unifying therapeutic target in myelofibrosis.

cancer biology↗

bioRxiv2026

The impact of crystallographic plane orientation as an unexplored terrain in hemocompatible material design

Thrombogenicity causes significant complications in the application of blood-contacting implants, requiring strategies to prevent adverse coagulation reactions. The thrombotic responses to the foreign surfaces are mainly driven by surficial factors such as surface energy, topography, and electrochemical interactions. Although anticoagulation therapies reduce the risks of clotting, patients might still encounter bleeding complications. Therefore, rather than high-risk anticoagulation therapies to counteract coagulation, it is essential to ensure hemocompatibility through the materials intrinsic properties. Endothelialization is crucial in preventing thrombotic complications, with various strategies explored for facilitating endothelial cell adhesion and proliferation. We investigated the impact of crystallographic anisotropy on endothelial and blood cell interactions on four main planes (A-, C-, M-, and R-planes) of single crystalline alumina (-Al2O3, sapphire). Employing advanced surface characterization techniques, including SIMS, KPFM and Zeta potential measurements, our study sheds light on the hemocompatibility of biomaterials considering anisotropic effects. We elucidated that the A-plane of alumina promotes endothelialization and suppresses platelet activation in contrast to other crystallographic planes. Our investigation into cell-surface interactions provides valuable insights and contributes to the advanced biomaterial design, ultimately leading to enhanced clinical outcomes.

bioengineering↗