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Vaskivskyi, V.

Publications and source records attributed to Vaskivskyi, V..

4 recordsLinked to original sources

Non-photosynthetic Plastid Replacement by a Primary Plastid in the Making

The integration of a cyanobacterium into a heterotrophic eukaryote gave rise to the primary plastid [~]1.5 Gya. This rare cyanobacterium-to-plastid transition has only been reported once more in Paulinella chromatophora [~]100 Mya. Unfortunately, the order and relative importance of organellogenesis events have been blurred by time in primary plastids and obscured by P. chromatophora becoming phototrophic. Here, we characterize the tripartite symbiosis in a benthic dinoflagellate (Sinophysis sp.) using diverse single-cell methods. Sinophysis houses a photosynthetic cyanobacterium closely interacting with an alphaproteobacterial endosymbiont. The cyanobacterium is in the intermediate stage of symbiont-to-organelle transition, with the host likely supporting it with metabolites and proteins, and controlling its cell division. Surprisingly, it seems to have replaced the hosts remnant non-photosynthetic plastid. Our results support mixotrophy, horizontal gene transfer, co-symbioses, and cell division control as early drivers of primary plastid origin and highlight the importance of protists for deciphering organellogenesis events.

evolutionary biology↗

PoSTcode: Probabilistic image-based spatial transcriptomics decoder

Realising the full potential of novel image-based spatial transcriptomic (IST) technologies requires robust and accurate algorithms for decoding the hundreds of thousand fluorescent signals each derived from single molecules of mRNA. In this paper, we introduce PoSTcode, a probabilistic method for transcript decoding from cyclic multi-channel images, whose effectiveness is demonstrated on multiple large-scale datasets generated using different versions of the in situ sequencing protocols. PoSTcode is based on a re-parametrised matrix-variate Gaussian mixture model designed to account for correlated noise across fluorescence channels and imaging cycles. PoSTcode is shown to recover up to 50% more confidently decoded molecules while simultaneously decreasing transcript mislabeling when compared to existing decoding techniques. In addition, we demonstrate its increased stability to various types of noise and tuning parameters, which makes this new approach reliable and easy to use in practice. Lastly, we show that PoSTcode produces fewer doublet signals compared to a pixel-based decoding algorithm.

bioinformatics↗

Spatial genomics maps the structure, character and evolution of cancer clones

Subclonality is a universal feature of cancers yet how clones grow, are spatially organised, differ phenotypically or influence clinical outcome is unclear. To address this, we developed base specific in situ sequencing (BaSISS). In fixed tissues, transcripts harbouring clone-defining mutations are detected, converted into quantitative clone maps and characterised through multi-layered data integration. Applied to 8 samples from key stages of breast cancer progression BaSISS localised 1.42 million genotype informative transcripts across 4.9cm2 of tissue. Microscopic clonal topographies are shaped by resident tissue architectures. Distinct transcriptional, histological and immunological features distinguish coexistent genetic clones. Spatial lineage tracing temporally orders clone features associated with the emergence of aggressive clinical traits. These results highlight the pivotal role of spatial genomics in deciphering the mechanisms underlying cancer progression.

cancer biology↗

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.

genomics↗