Biology subjects

Hoefflin, R.

Publications and source records attributed to Hoefflin, R..

3 recordsLinked to original sources

bioRxiv2026

Spatial analysis reveals the evolving organization of low-grade and high-grade IDH-mutant glioma

Adult diffuse gliomas are comprised of malignant cell states interwoven with the non-malignant brain microenvironment. Here we combine spatial transcriptomics and spatial proteomics of IDH-mutant gliomas to define organizational principles across histological grades. In low-grade tumors, spatial organization arises from underlying nonmalignant brain structures. For example, we classify low-grade tumor regions as embedded into white matter and identify a sharp white-grey matter junction that restricts cortical invasion and is associated with marked changes in tumor composition and cellular phenotypes. This junction is preferentially traversed by oligodendrocyte progenitor (OPC)-like malignant cells, which may drive tumor expansion. In contrast, intermediate-grade tumors are largely disorganized, with few recurring pairwise interactions between cancer cell states and TME cell types. In high-grade tumors, hypoxia/necrosis-associated global structure begins to emerge, reminiscent of IDH-wildtype glioblastoma. Together, these findings reveal two independent axes of glioma spatial organization--from brain anatomy-driven organization in low-grade tumors to hypoxia-associated structure in high-grade tumors--and establishes a framework that links tumor grade to recurrent spatial associations between cell states and cell types.

cancer biology↗

bioRxiv2024

The Curated Cancer Cell Atlas: comprehensive characterisation of tumours at single-cell resolution

Single-cell RNA-seq (scRNA-seq) has transformed the study of cancer biology. Recent years have seen a rapid expansion in the number of single-cell cancer studies, yet most of these studies profiled few tumours, such that individual datasets have limited statistical power. Combining the data and results across studies holds great promise but also involves various challenges. We recently began to address these challenges by curating a large collection of cancer scRNA-seq datasets, and leveraging it for systematic analyses of tumor heterogeneity. Here we significantly extend this repository to 124 datasets for over 40 cancer types, together comprising 2,822 samples, with improved data annotations, visualisations and exploration. Utilising this vast cohort, we systematically quantified context-dependent gene expression and proliferation patterns across cell types and cancer types. These data, annotations and analysis results are all freely available for exploration and download via the Curated Cancer Cell Atlas (3CA) website (https://www.weizmann.ac.il/sites/3CA/), a central source of data and analyses for the cancer research community that opens new avenues in cancer research.

cancer biology↗

bioRxiv2023

Integrative spatial analysis reveals a multi-layered organization of glioblastoma

Glioma contains malignant cells in diverse states. Hypoxic regions are associated with a unique histology of pseudopalisading cells, while other regions appear to have limited histological organization, reflecting the diffuse nature of glioma cells. Here, we combine spatial transcriptomics with spatial proteomics and novel computational approaches to define glioma cellular states at high granularity and uncover their organization. We find three prominent modes of cellular organization. First, cells in any given state tend to be spatially clustered, such that tumors are composed of small local environments that are each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. Despite the unique composition of each tumor, this pairing of states remains largely consistent across tumors. Third, the pairwise interactions that we detect collectively define a global architecture composed of five layers. Hypoxia appears to drive this 5-layered organization, as it is both associated with unique states of surrounding cells and with a long-range organization that extends from the hypoxic core to the infiltrative edge of the tumor. Accordingly, tumor regions distant from any hypoxic foci and tumors that lack hypoxia such as IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of gliomas at the resolution of cellular states and highlight the role of hypoxia as a long-range tissue organizer.

cancer biology↗