Biology subjects

Kroeger, N.

Publications and source records attributed to Kroeger, N..

3 recordsLinked to original sources

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↗

bioRxiv2024

Gliding motility of the diatom Craspedostauros australis correlates with the intracellular movement of raphid-specific myosins

Raphid diatoms are one of the few eukaryotes capable of gliding motility, which is remarkably fast and allows for quasi-instantaneous directional reversals. Besides other mechanistic models, it has been suggested that an actomyosin system provides the force for diatom gliding. However, in vivo data on the dynamics of actin and myosin in diatoms are lacking. In this study we demonstrate that the raphe-associated actin bundles required for diatom movement do not exhibit a directional turnover of subunits and thus their dynamics do not contribute directly to force generation. By phylogenomic analysis we identified four raphid diatom-specific myosins in Craspedostauros australis (CaMyoA-D) and investigated their in vivo localization and dynamics through GFP-tagging. Only CaMyoB-D but not CaMyoA exhibited coordinated movement during gliding, consistent with a role in force generation. The characterization of raphid diatom-specific myosins lays the foundation for unraveling the molecular mechanisms that underlie the gliding motility of diatoms.

cell biology↗

bioRxiv2023

Diatom adhesive trail proteins acquired by horizontal gene transfer from bacteria serve as primers for marine biofilm formation

O_LIBiofilm-forming benthic diatoms are key primary producers in coastal habitats, where they frequently dominate sunlit submerged and intertidal substrata. The development of a unique form of gliding motility in raphid diatoms was a key molecular adaptation that contributed to their evolutionary success. Gliding motility is hypothesized to be driven by an intracellular actin-myosin motor and requires the secretion of polysaccharide- and protein-based adhesive materials. To date, the structure-function correlation between diatom adhesives utilized for gliding and their relationship to the extracellular matrix that constitutes the diatom biofilm is unknown. C_LIO_LIProteomics analysis of the adhesive material from Craspedostauros australis revealed eight novel, diatom-specific proteins. Four of them constitute a new family of proteins, named Trailins, which contain an enigmatic domain termed Choice-of-Anchor-A (CAA). Immunostaining demonstrated that Trailins are only present in the adhesive trails required to generate traction on native substrata, but are absent from the extracellular matrix of biofilms. Phylogenetic analysis and Protein 3D structure prediction suggests that the CAA-domains in Trailins were obtained from bacteria by horizontal gene transfer, and exhibit a striking structural similarity to ice-binding proteins. C_LIO_LIOur work advances the understanding of the molecular basis for diatom underwater adhesion and biofilm formation providing evidence that there is a molecular switch between proteins required for initial surface colonization and those required for 3D biofilm matrix formation. C_LI

plant biology↗