Camargo, S. | Search bioRxiv

bioRxiv2026

A pan-cancer single-cell atlas of pericytes

Pericytes display marked tissue-specific transcriptional identities, raising the question of whether tumour-associated pericytes converge towards shared adaptive states across cancers. Here, we built a pan-cancer single-cell RNA sequencing atlas of pericytes, integrating nearly four million cells across nine tissues, complemented by spatial transcriptomic analyses. Despite their physiological diversity, pericytes were recurrently expanded in tumours and converged on a common transcriptional program, the tumour-associated pericyte signature (TAPS). TAPS robustly identified pericytes across datasets, outperforming canonical markers in tumour contexts. Tumour-associated pericytes further diversified into specialised states including extracellular matrix (ECM)-associated and interferon (IFN)-responsive programs, which occupy mutually exclusive tumour ecosystems. ECM-associated pericytes were enriched in desmoplastic, fibroblast-rich regions and were associated with adverse clinical outcomes across multiple cancer types. IFN-responsive pericytes accumulated in inflammatory niches, with macrophages implicated as candidate drivers of specialisation. Together, our multi-layered analysis defines convergent and specialised tumour-associated pericyte programs across human cancers.

cancer biology↗

bioRxiv2023

Heterologous expression of genes from a heterocystous cyanobacterial endosymbiont highlights organic carbon exchange with its diatom host

A few genera of diatoms are widespread and thrive in low nutrient waters of the open ocean due to their close association with N2-fixing, filamentous heterocyst-forming cyanobacteria. In one of these symbioses, the symbiont, Richelia euintracellularis, has penetrated the cell envelope of the host, Hemiaulus hauckii, and lives inside the host cytoplasm. How the partners interact, including how the symbiont sustains high rates of N2 fixation is unstudied. Since R. euintracellularis has evaded isolation, heterologous expression of genes in model laboratory organisms was performed to identify the function of proteins from the endosymbiont. Gene complementation of a cyanobacterial invertase mutant and expression of the protein in Escherichia coli showed that R. euintracellularis HH01 possesses a neutral invertase that splits sucrose producing glucose and fructose. Several solute binding proteins (SBPs) of ABC transporters encoded in the genome of R. euintracellularis HH01 were expressed in E. coli and their substrates were characterized. The selected SBPs directly linked the host as the source of several substrates, e.g., sugars (sucrose, galactose), amino acids (glutamate, phenylalanine) and a polyamine (spermidine), to support the cyanobacterial symbiont. Finally, transcripts of genes encoding the invertase and SBPs were consistently detected in wild populations of H. hauckii collected from multiple stations and depths in the western tropical North Atlantic. Our results support the idea that the diatom host provides the endosymbiotic cyanobacterium with organic carbon to fuel N2 fixation. This knowledge is key to understand the physiology of the globally significant H. hauckii-R. euintracellularis symbiosis. SIGNIFICANCEDiatom diazotroph associations (DDAs) between diatoms and N2-fixing bacteria (diazotrophs) have a relevant impact on N2 fixation-based production, but the mechanisms underlying their integrated N2 and CO2 fixation remain unstudied. In the association between the diatom Hemiaulus hauckii (host) and the N2-fixing, heterocyst-forming cyanobacterium Richelia euintracellularis (endosymbiont), the cyanobacterium is uncultivable. Here we used heterologous expression of genes from the endosymbiont to identify the function of proteins involved in the utilization of organic carbon from the host. The importance of these proteins was also confirmed by estimating gene expression in environmental samples. Our results show that the metabolisms of the symbiotic partners are integrated allowing the host to sustain the physiology of the endosymbiont for an important ecological role.

molecular biology↗