Biology subjects

Matos, G. M.

Publications and source records attributed to Matos, G. M..

3 recordsLinked to original sources

bioRxiv2026

Single cell analysis reveals molecular traits of pediatric lymphoma resistant subclones

The cause of refractory/relapse (R/R) in pediatric lymphoma is unclear. We hypothesized that a stem-like, chemoresistance lymphoma subclone may contribute to R/R. Combining single cell RNA sequencing (scRNA-seq) and immune receptor sequencing (scVDJ-seq) on freshly acquired pediatric non-Hodgkin lymphoma (pNHL n=10), Hodgkin lymphoma (pHL n=5), and 10 reactive lymph nodes from adults or children (a/pReLy), we discovered pediatric-specific progenitor-like lymphocytes, whose cellular program was enriched in pNHL subclones emerging late during clonal evolution, accompanied by loss of immune receptor expression. R-CHOP target gene expression indicated that these subclones may escape first-line treatment, and suggested MSI2, an RNA binding protein, as a potential target. In pHL, the progenitor-like program was found in the tumor microenvironment (TME) but not Hodgkin cells which, during relapse, were myeloid-like and accompanied by CD74highCCL5+ CD8 T cells. In summary, we discovered R/R associated lymphoma subclones in pediatric lymphoma and potential ways to eradicate them. Key messagesO_LIProgenitor-like lymphocytes are uniquely found in pediatric reactive lymph nodes, but not in adults. C_LIO_LIResistant subclones from pNHL acquire progenitor-like program and share MSI2 expression. C_LIO_LIRelapsed Hodgkin cells are monocyte-like and recruit CD74highCCL5+ CD8 T cells. C_LI

cancer biology↗

bioRxiv2026

Comprehensive genomic analysis of Trypanosoma rangeli reveals key insights into the biology and evolution of this non-virulent American mammalian trypanosome

BackgroundTrypanosoma rangeli is a non-virulent hemoflagellate protozoan parasite that infects mammals, including humans, in Central and South America. It is primarily transmitted through the bites of triatomine bugs and shares an overlapping geographical distribution with T. cruzi, as well as triatomine vectors and mammalian hosts, and various shared surface antigens. The life cycle of T. rangeli differs from those of other human-infecting trypanosomes, such as T. cruzi and T. brucei, and the molecular mechanisms underlying host-parasite and host-vector interactions are not well understood, demanding improved molecular and genomic resources. ResultsThe use of a hybrid approach to sequence and assemble the T. rangeli genome, complemented by transcriptomics and proteomics for functional gene annotation, led to the generation of the near-complete genome sequence of the parasite. Detailed intra- and inter-specific comparative genomics allowed analysis of polymorphisms, genome structure and improved resolution of genes coding for important surface molecules such as Mucins, TASV and GP63. ConclusionsThe improved T. rangeli genome assembly, combined with comparative genomics has yielded novel biological insights. These included the first description of a metalloprotease activity, attributed to specific GP63 genes that are absent in Leishmania species. In addition, a TASV gene family that is absent in T. cruzi was identified, which indicates a possible role in the T. rangeli infection process.

microbiology↗

bioRxiv2021

Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure.

Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was progressive, gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.

microbiology↗