Biology subjects

Janda, C.

Publications and source records attributed to Janda, C..

3 recordsLinked to original sources

bioRxiv2026

Lineage-associated tumor cell states predict outcome and guide immunotherapeutic target selection in pediatric osteosarcoma

Osteosarcoma is a highly heterogeneous primary bone malignancy that predominantly affects adolescents and young adults, and robust prognostic biomarkers and effective targeted therapies remain lacking. While single-cell transcriptomics has begun to resolve tumor composition, a tumor cell-intrinsic framework linking transcriptional states to clinical outcome and therapeutic targeting is not established. Here, we present a single-cell transcriptomic analysis of pediatric osteosarcoma, integrating 22 samples across 18 patients spanning six diagnostic, six post-treatment, and ten metastatic lesions profiled using complementary sequencing platforms. Using non-negative matrix factorization, we identify recurrent lineage-associated transcriptional programs that define osteoblastic-like, chondroblastic-like, and fibroblastic-like tumor cell states. These programs show overlapping activity across tumor cells, indicating that tumor cell states are not strictly discrete. Strikingly, combined osteoblastic-like and chondroblastic-like program activity is associated with poorer overall survival, a finding validated across two independent bulk RNA-sequencing cohorts. These tumor cell states are further linked to distinct immune microenvironmental compositions. Mapping candidate immunotherapeutic targets at single-cell resolution reveals variable expression across tumor cell states, supporting state-informed strategies for CAR T cell targeting. Together, our findings establish a tumor cell state framework that links osteosarcoma heterogeneity to clinical outcome and provides a basis for patient stratification and the development of state-informed therapeutic strategies in pediatric osteosarcoma.

Cancer Biology↗

bioRxiv2025

Mechanisms of dexamethasone-induced bone toxicity in developing bone: a single-cell perspective

AbstractGlucocorticoids, such as dexamethasone, are essential for treating severe childhood conditions, including cancer, organ transplantation, and inflammatory disorders. However, their long-term use can impair bone development, posing risks to pediatric bone health, which is vital for lifelong skeletal integrity. A mechanistic insight on how glucocorticoids negatively impact bone could improve decision-making in patient care to improve the quality of life for pediatric cancer patients and survivors. In this study, we aimed to elucidate the molecular mechanisms underlying dexamethasone-induced bone toxicity in developing bones using single-cell transcriptomics. We treated skeletally immature C57BL/6JRj mice with dexamethasone for 28 days, and assessed the bone architecture with micro-computed tomography, and characterized bone and bone marrow cells from the femurs using single-cell RNA sequencing. Our findings revealed a marked reduction in osteoblast and chondrocyte cell populations and impaired function of pre-osteoblasts. Additionally, dexamethasone adversely affected B cell subsets, significantly depleting early B cell progenitors while allowing some further developed immature B cells to persist. These cellular changes were accompanied by reduced longitudinal bone growth, compromised bone architecture, and increased bone fragility at the highest doses of dexamethasone. Interestingly, unlike observations in adults, dexamethasone did not enhance osteoclast activity in our model. Overall, our study suggests that the adverse effects of dexamethasone on bone development are primarily due to its impact on osteoblastic, chondroblastic and B cell lineages, disrupting the critical signaling crosstalk between the cells necessary for bone development and hematopoiesis. Layman summaryGlucocorticoids, like dexamethasone, are vital for treating severe childhood illnesses but can harm bone development when used long-term. This study investigated how dexamethasone affects bone health in young mice. Using advanced techniques, we found that dexamethasone reduced key bone-building cells (osteoblasts and chondrocytes) and weakened their function. It also disrupted immune cell development in the bone marrow, especially early B cells. These changes led to weaker, more fragile bones without increasing bone breakdown, unlike in adults. The findings highlight the need to carefully balance treatment benefits and risks for children to protect their bone health and overall well-being.

cancer biology↗

bioRxiv2024

Integrin-activating Yersinia protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets

Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells (ASC)1,2. Here, we show that interaction between Matrigels major component Laminin111 with epithelial 6{beta}1-integrin is crucial for this process. The outer membrane protein Invasin of Yersinia is known to activate multiple integrin-{beta}1 complexes, including integrin-6{beta}1. A C-terminal integrin-binding fragment of Invasin, coated on culture plates, mediated gut epithelial cell adhesion. Addition of organoid growth factors allowed multi-passage expansion in 2D. Polarization, junction formation and generation of enterocytes, goblet cells, Paneth cells, and enteroendocrine cells was stable over time. Sustained expansion of other human-, mouse-, and even snake epithelia was accomplished under comparable conditions. The 2D organoid sheet format holds advantages over the 3D in gel format in terms of imaging, accessibility of basal and apical domains and automation for high throughput screening. Invasin represents a fully defined, affordable, versatile, and animal-free complement to Matrigel/BME.

cell biology↗