Biology subjects

Bejar, M. T.

Publications and source records attributed to Bejar, M. T..

3 recordsLinked to original sources

bioRxiv2024

Improving the annotation of amino acid biosynthesis pathways: GapMind 2024

We previously described GapMind, an automated web-based tool for annotating amino acid biosynthesis pathways in bacterial and archaeal genomes. We used GapMind to identify gaps in biosynthetic pathways and systematically used comparative genomics and high-throughput genetics to identify candidate genes to fill these gaps. We confirmed the activity of ten of the proposed enzymes by using cross-species complementation assays. Highlights include a novel route to glycine, two families that can replace phosphoserine phosphatase, an alternative N-succinyl-L,L-diaminopimelate desuccinylase, an alternative N-acetylornithine deacetylase, and a bifunctional MetB/MetC. We updated GapMind to include these additional enzymes. Across 208 prokaryotes that have high-quality genomes and can grow in minimal media, the average number of unexplained missing steps or gaps in amino acid biosynthesis dropped from 1.4 per genome to 0.7 per genome. The majority of remaining gaps involve the gain or loss of phosphate groups.

microbiology↗

bioRxiv2024

Pre-cancerous Niche Remodelling Dictates Nascent Tumour Survival

Interactions between mutant cells and their environment play a key role in determining cancer susceptibility. However, our understanding of how the pre-cancer microenvironment contributes to early tumorigenesis remains limited. Here, we show that newly emerging tumours at their most incipient stages shape their microenvironment in a critical process that determines their survival. Analysis of nascent squamous tumours in the upper gastrointestinal tract of the mouse reveals that the stress response of early tumour cells instructs the underlying mesenchyme to form a supportive "pre-cancer niche", which dictates the long-term outcome of epithelial lesions. Stimulated fibroblasts beneath emerging tumours activate a wound healing response that triggers a dramatic remodelling of the underlying extracellular matrix, resulting in the formation of a fibronectin-rich stromal scaffold that promotes tumour growth. Functional heterotypic 3D culture assays and in vivo grafting experiments, combining carcinogen-free healthy epithelium and tumour-derived stroma, demonstrate that the pre-cancerous niche alone is sufficient to confer tumour properties to healthy epithelial cells. We propose a model where both mutations and the stromal response to genetic stress defines the likelihood of early tumours to survive and progress towards more advanced disease stages.

cancer biology↗

bioRxiv2021

Defining the transcriptional signature of esophageal-to-skin lineage conversion

The ability of epithelial cells to rewire their cell fate program beyond their physiological repertoire has become a new paradigm in stem cell biology. This plasticity leaves behind the concept of strict stem cell hierarchies, opening up new exciting questions about its limits and underlying regulation. Here we developed a heterotypic 3D culture system to study the mechanisms modulating changes in the identity of adult esophageal epithelial cells. We demonstrate that, when exposed to the foreign stroma of adult skin, esophageal cells transition towards hair follicle identity and architecture. Heterotypic transplantation experiments recapitulated this cell fate conversion process in vivo. Single-cell RNA sequencing and histological analysis, capturing the temporality of this process, reveal that most esophageal cells switching towards skin identity remain in an intermediate state marked by a transient regenerative profile and a particularly strong hypoxic signature. Inhibition of HIF1a establishes the central role of this pathway in regulating epithelial cell plasticity, driving cells away from their transition state in favor of cell fate conversion.

cell biology↗