bioRxiv Science⌕ Search

Biology subjects

Reyes, O.

Publications and source records attributed to Reyes, O..

2 recordsLinked to original sources

Palaeogenomics reveals 1,500 years of population history of the peoples of the Chonos Archipelago, Chile.

The Chonos archipelago, located in northwestern Chilean Patagonia, was historically inhabited by an Indigenous sea-faring population known to the European colonists as the "Chono". Previous research has contextualized the human occupation of this region with radiocarbon dates and ancient mitochondrial genomes, offering a partial perspective on the history of its inhabitants. Here we present a paleogenomic analysis of 20 ancient human individuals from 6 archaeological sites, dated between 1,600-50 years before present (BP). We successfully captured over 100,000 SNPs from 15 of 20 individuals and recovered 12 full mitogenomes. All individuals presented unadmixed Indigenous South American ancestry and formed a separated genetic cluster relative to other ancient and modern South American genomes, indicating a unique Chonos ancestry. This Chonos ancestry falls within a broader cluster of late-Holocene Patagonian ancestry, most similar to the Kawesqar peoples who neighbour to the south. Within the Chonos, we distinguish a northern and southern ancestry cluster. The northern Chonos cluster exhibits some genetic connections to the present-time inhabitants of the neighbouring island of Chiloe, who are connected to Huilliche Indigenous history. Our findings reveal a point of contact between southern Chonos/Patagonian ancestry to the south and Mapuche ancestry to the north, and confirm that sea-faring subsistence was a knowledge transferred between Patagonian peoples.

genomics↗

Spliceosomic dysregulation unveils NOVA1 as an actionable therapeutic target in pancreatic neuroendocrine tumors

Dysregulation of the splicing machinery is emerging as a hallmark in cancer due to its association with multiple dysfunctions in tumor cells. Inappropriate function of this machinery can generate tumor-driving splicing variants and trigger oncogenic actions. However, its role in pancreatic neuroendocrine tumors (PanNETs) is poorly defined. In this study we aimed to characterize the expression pattern of a set of splicing machinery components in PanNETs, and their relationship with aggressiveness features. A qPCR-based array was first deployed to determine the expression levels of components of the major (n=13) and minor spliceosome (n=4) and associated splicing factors (n=27), using a microfluidic technology in 20 PanNETs and non-tumoral adjacent samples. Subsequently, in vivo and in vitro models were applied to explore the pathophysiological role of NOVA1. Expression analysis revealed that a substantial proportion of splicing machinery components was altered in tumors. Notably, key splicing factors were overexpressed in PanNETs samples, wherein their levels correlated with clinical and malignancy features. Using in vivo and in vitro assays, we demonstrate that one of those altered factors, NOVA1, is tightly related to cell proliferation, alters pivotal signaling pathways and interferes with responsiveness to drug treatment in PanNETs, suggesting a role for this factor in the aggressiveness of these tumors and its suitability as therapeutic target. Altogether, our results unveil a severe alteration of the splicing machinery in PanNETs and identify the putative relevance of NOVA1 in tumor development/progression, which could provide novel avenues to develop diagnostic biomarkers and therapeutic tools for this pathology.

cancer biology↗