Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional profiling of healthy versus cystic fibrosis human endometrial organoids upon hormonal exposure

ABSTRACT: Female cystic fibrosis (CF) patients are confronted with fertility deficiency, experiencing difficulties in getting pregnant. Underlying reasons remain elusive. In particular, it has only poorly been studied whether the endometrium, the inner lining of the womb and crucial tissue for embryo implantation, plays a role. One main reason is the lack of reliable and tractable study models given the major technical and ethical hurdles to study events that occur hidden in the womb.To overcome this, we established an endometrium CF organoid model. We applied bulk RNA sequencing on these organoids derived form endometrium of women affected by CF and of healthy women. These endometrial organoids (EO) were exposed to hormones to mimic different phases of the menstrual cycle. The proliferative phase was mimicked by exposing the EO to estradiol (+E2), while the (mid-)secretory phase was mimicked by estradiol, progesterone, cyclic AMP and XAV-939 (Wnt inhibitor) (EPCX) exposure of EO. As a control, we sequenced healthy and CF EO not exposed to hormones (EOM).

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

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PROVIDER: E-MTAB-14456 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): E-MTAB-14455

REPOSITORIES: biostudies-arrayexpress

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Project description:It has been recognised for a long time that cell surface glycans plays a vital role in the biological process and their altered form can lead to cancer. However, the molecular details and regulatory mechanism between the glycans and cancer is yet not clear. Over the past decade mass spectrometry-based techniques has become a prominent method for analysing glycans especially N-glycan matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). It is a powerful technique that combines mass spectrometry with histology, enabling the visualisation and label free detection of N-linked glycans on a single tissue section. Here, we carried out N-glycan MALDI MSI on six endometrial cancer (EC) formalin fixed paraffin embedded (FFPE) tissue sections including the adjacent normal endometrium, and tissue microarrays (TMA) consisting of 8 EC patients with lymph node metastasis (LNM) and 20 without LNM. By doing that several m/z values were detected that can significantly distinguish normal endometrium from cancerous. Also, detected a m/z value that can discriminate the primary tumour with LNM from those without. Identification of those discriminative m/z values was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose in tumour regions compared to normal with AUC ranges from 0.85-0.99. Whereas, complex N-glycans were detected in lower abundance with AUC ranges from 0.03-0.28. Comparison of N-glycans between the primary tumours with LNM and without LNM indicates reduced abundance of a complex core-fucosylated N-glycan in patients with metastasis relative to without. In summary, N-glycan MALDI MSI can be used to characterize the cancerous endometrium from the normal, also patients with LNM from those without. Identification of those discriminative m/z values was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).

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Transcriptional profiling of healthy versus cystic fibrosis human endometrial organoids upon hormonal exposure

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