Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of human induced pluripotent stem cell-derived intestinal tissue (xenografts) with normal adult human colon (NanoString GeoMX DSP)

ABSTRACT: Tissue samples from human induced pluripotent stem cell-derived intestinal tissue (iPSC-derived intestinal progenitors seeded onto collagen hydrogels) which were transplanted subcutaneously in mice. Mice were sacrificed and tissues were collected after 2, 3 or 4 weeks following engraftment. The tissues were sectioned onto slides and then profiled using NanoString GeoMX DSP (cancer transcriptome atlas). Normal human colon tissue was also profiled as a reference. In both cases, slides were stained for nuclei and cytokeratin. ROIs were selected from in vivo tissue to represent the entire tissue present. For colon reference tissue, crypt apices and bases were selected. Automated segmentation of each ROI using cytokeratin status (positive / negative) was also performed. Gene expression of all genes was evaluated to determine the most differentially expressed (for reference data). These genes and other intestinal genes were specifically investigated further on in vivo samples to ascertain areas of similarity to adult colon and furthermore to demonstrate maturation across timepoints.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: William Dalleywater

PROVIDER: E-MTAB-13834 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). CRC is known to display glycosylation alterations. Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer, such as cell signaling and adhesion, and may can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples from patients with tumors in the right or left colon and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left side of the colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right- and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways, regardless of tumor location.

Dataset Information

Comparison of human induced pluripotent stem cell-derived intestinal tissue (xenografts) with normal adult human colon (NanoString GeoMX DSP)

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