Biology subjects

Kaukinen, K.

Publications and source records attributed to Kaukinen, K..

3 recordsLinked to original sources

bioRxiv2026

Celiac disease patient derived iPSC small intestinal epithelial cells are more persistent under cytokine stimuli than healthy control cells

Background & AimsCeliac disease is a wheat-induced immune-mediated enteropathy. Intestinal organoid models for adult stem cell-based celiac disease exist, but planar intestinal models derived from celiac disease patients that would allow direct assessment from both sides of the epithelium have been lacking. We aimed to bridge this gap by setting up a two-dimensional in vitro model based on small intestinal epithelial cells (SIECs) derived from induced pluripotent stem cells (iPSC) from celiac disease patients. MethodsIPSCs from celiac disease and control patients were sequentially differentiated towards SIECs. The models applicability was tested under cytokine stimuli. ResultsCeliac disease and control patient iPSCs matured similarly towards SIECs. However, they had inherent gene expression differences in inflammation- and immune-related genes, such as IRF1 and HLA-DRB1. Both iPSC-SIECs responded in a SIEC-specific manner to the cytokine stimulation. The response in celiac disease iPSC-SIECs was attenuated compared with that of control iPSC-SIECs. ConclusionsThe data confirm that iPSC-derived SIECs represent an appropriate platform for studying inflammation-associated enteropathies, such as celiac disease, but also suggest that there might be inherent patient-specific or cell type-specific differences in the responses.

cell biology↗

bioRxiv2024

eDNA sampling systems for salmon ecosystem monitoring

Environmental DNA (eDNA) is transforming the way aquatic ecosystems are monitored and managed by scientists, resource managers, ENGOs, First Nations communities, and citizen scientists alike. However, the lack of sampling systems enabling high filtration volumes and rapid sample collection in the field have thus far hindered broad scale eDNA studies in the ocean specifically for small and medium scale organizations. To overcome these challenges, several modular water sampling systems that utilize hollow-membrane filtration cartridges were developed by RKS laboratories and tested by the Fisheries and Oceans, Canada, Molecular Genetics Laboratory. Compared to Sterivex filters, an industry standard for eDNA filtration, the hollow-membrane filtration cartridges allowed for a six-fold increase in filtration volume and threefold increase in filtration speed. The field sampling systems, which combine pumps, a programmable controller, an air pump, an ozone generator, and up to eight filters at once, enabled efficient direct eDNA filtration from diverse aquatic environments, from creeks to the open ocean. To evaluate ease of deployment, we present the results of a three day workshop where technical staff of an Indigenous resource management organization, without any prior knowledge in eDNA sampling, were trained and performed independent eDNA sample collection. The samples were analyzed by metabarcoding and qPCR to reveal the distributions of salmon and other species co-occurring in salmon ecosystems, from large ephemeral predators, to the planktonic prey of salmon, even including their pathogens. In this example study, we further observed a substantial shift in community composition in the vicinity of aquaculture facilities where marine species associated with aquaculture feed were detected in freshwater at high relative abundance. This study demonstrates how these sampling systems provide an efficient entry point for small and medium scale organizations to utilize eDNA to fulfill their research and monitoring objectives.

genomics↗

bioRxiv2018

Clustering based approach for population level identification of condition-associated T-cell receptor β-chain CDR3 sequences

MotivationDeep immune receptor sequencing, Repseq, provides unprecedented opportunities to identify condition-associated T-cell clones, represented by T-cell receptor (TCR) CDR3 sequences. TCR profiling has potential value for increasing immunopathological understanding of various diseases, and holds considerable clinical relevance. However, due to the immense diversity of the immune repertoire, identification of condition relevant TCR CDR3s from total repertoires has so far been limited either to mostly \"public\" CDR3 sequences, which are shared across unrelated individuals, or to comparisons of CDR3 frequencies from multiple samples from the same individual. A methodology for the identification of condition-associated TCR CDR3s by population level comparison of groups of Repseq samples is currently lacking.\n\nResultsWe implemented a computational pipeline that allows population level comparison of Repseq sample groups at the level of the immune repertoire sub-units that are shared across individuals. These sub-units (or sub-repertoires) represent shared immuno-genomic features across individuals that potentially encode common signatures in the immune response to antigens. The method first performs unsupervised clustering of CDR3 sequences within each sample based on their similarity in nucleotide or amino acid subsequence frequency. Next, it finds matching clusters across samples, the immune sub-repertoires, and performs statistical differential abundance testing at the level of the identified sub-repertoires. We applied the method on total TCR CDR3{beta} Repseq datasets of celiac disease patients in gluten exposed and unexposed conditions, as well as on public dataset of yellow fever vaccination volunteers before and after immunization. The method successfully identified condition-associated CDR3{beta} sequences, as evidenced by considerable agreement of TRBV-gene and positional amino acid usage patterns in the detected CDR3{beta} sequences with previously known CDR3{beta} species relevant to celiac disease. The method also recovered significantly high numbers of previously known CDR3{beta} sequences, relevant to each condition than would be expected by chance. We conclude that immune sub-repertoires of similar immuno-genomic features, shared across unrelated individuals, encode common immunological information. Moreover, they can serve as viable units of population level immune repertoire comparison, serving as proxy for identification of condition-associated CDR3 sequences.

bioinformatics↗