Biology subjects

Kusumbe, A.

Publications and source records attributed to Kusumbe, A..

4 recordsLinked to original sources

bioRxiv2026

Bone Lymphatic Endothelial Cells Form a Distinct Skeletal Population and Drive Skeletal Repair

Bone regeneration relies on specialized vascular niches, yet the contribution of lymphatic vessels across distinct skeletal sites remains poorly understood. Here, we identify bone lymphatics as an essential component of the regenerative microenvironment in the mandible and long bones. We demonstrate that bone lymphatic endothelial cells (LECs) constitute a specialized endothelial population that is transcriptionally and spatially distinct from periosteal LECs. During skeletal repair, bone LECs reactivate a regenerative transcriptional programme, and promote mandibular and fracture healing. In osteonecrosis of the jaw and periodontitis, bone lymphatic-associated signalling is disrupted, identifying impaired lymphatic function as a shared feature of mandibular disease. Therapeutic activation of VEGFC-FLT4 signalling during injury or mandibular disease restores lymphangiogenesis, enhances osteogenesis, and markedly improves bone regeneration. Together, our findings advance the paradigm-shifting role of bone lymphatics positive regulators of bone regeneration and identify lymphatic activation as a promising therapeutic strategy to enhance bone regeneration in mandibular diseases.

cell biology↗

bioRxiv2025

Wnt-presenting materials sustain H3K14-acetylation in human skeletal stem cells for tissue engineering and bone repair

Engineering functional tissues for transplantation requires insight into epigenetic mechanisms that regulate stem cell fate. We have developed the Wnt-induced osteogenic tissue model (WIOTM), a platform that recapitulates human osteogenesis, and identified acetylation of histone H3 at lysine 14 (H3K14ac) as a critical epigenetic regulator in human skeletal stem cells (hSSCs). In WIOTM, localized Wnt signals drive asymmetric cell division (ACD), yielding a proximal hSSC with high H3K14ac and a distal daughter with reduced H3K14ac that migrates into the 3D collagen matrix and initiates osteogenic differentiation. Disrupting H3K14ac in hSSCs abrogates ACD and WIOTM formation. To test whether hSSCs maintain H3K14ac in vivo, we formed the WIOTM on Wnt-functionalized polymer bandages and transplanted them into calvarial defects. The WIOTM contributed to bone repair, and human cells adjacent to the bandages retained high H3K14ac despite the injury environment. These findings establish WIOTM as both a mechanistic and translational platform for regenerative medicine.

cell biology↗

bioRxiv2024

Stimulation of NCAM1-14.3.3.ζδ-derived Peptide Interaction Fuels Angiogenesis and Osteogenesis in Ageing

The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent new endogenous anabolic NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of new bone. Moreover, the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

cell biology↗

bioRxiv2021

A Simple Ultrafast Multicolor Immunolabelling and Clearing Approach for Whole-Organ and Large Tissue 3D Imaging

High-resolution whole-organ imaging of cleared tissues captures cellular and molecular insights within the intact tissue and tumour microenvironments. However, current immunolabelling and clearing methods are complicated and time-consuming; extending to several weeks. Here, we developed Simple Ultrafast Multicolor Immunolabelling and Clearing or SUMIC, a method that enables multicolor immunolabelling and clearing of whole murine organs and human tissues within 2 to 2.5 days. Moreover, SUMIC is simple, robust, non-hazardous and versatile comprising antigen retrieval, permeabilization, collagenase-based digestion, immunolabelling, dehydration, and clearing. SUMIC permits quantitative and singlecell resolution analysis and detection of rare cells in whole organs, for example, round SMA positive cells in the thymus. Upon volumetric imaging, SUMIC-processed samples retain normal tissue architecture and can be used for paraffin-embedding and histology. We employed the SUMIC method for whole-organ mapping of lymphatic vessels across different ages and organs. This analysis revealed the expansion of lymphatic vessels in endocrine tissues but not in any other organs with aging. Hence, SUMIC will accelerate discoveries compared to other whole organ imaging pipelines.

physiology↗