E4e94fff-a46f-4a63-a2e8-96ace38b89c4 - samples
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ABSTRACT:
PROVIDER: EGAD00001006417 | EGA |
REPOSITORIES: EGA
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Project description:Background & Aims: Tissue metaplasia is uncommon in adults because established cis-element programs resist rewiring. In Barrett’s esophagus, the distal esophageal mucosa acquires predominantly intestinal character, with notable gastric features, and is predisposed to develop invasive cancers. We sought to understand the chromatin underpinnings of Barrett’s metaplasia and why it commonly displays simultaneous gastric and intestinal properties. Methods: We profiled cis-regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Mutations in Barrett’s esophagus were examined in relation to tissue-specific enhancer landscapes using a random-forest machine learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett’s biopsy specimens using the assay for transposase-accessible chromatin (ATAC-seq). We used one- and two-color immunohistochemistry to examine protein expression of tissue-restricted genes. Results: Barrett’s esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis-elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett’s metaplasia co-express gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins, CLDN18, and a novel gastric marker, ANXA10, revealed extensive tissue and sub-clonal heterogeneity of dual stomach-intestinal cell states. Conclusions: These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett’s esophagus. Pervasive intra-gland variation argues against stem-cell governance of this phenotype.
2021-06-03 | GSE97178 | GEO
Project description:The upper gastrointestinal tract consisting of the esophagus, stomach and duodenum controls food transport, digestion, nutrient uptake and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly defined their distinct cell types. We identified a quiescent COL17A1high stem/progenitor cell population within the basal cell layer of the esophagus and detected substantial gene expression differences between identical cell types of the human and mouse stomach. Selective and high expression of BEST4, CFTR, guanylin and uroguanylin identified the rare duodenal BCHE cells, which likely mediate high-volume fluid secretion due to continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Unexpectedly, the previously uncharacterized serotonin-producing enterochromaffin cells in the antral stomach significantly differ in gene expression from the duodenal enterochromaffin cells. We furthermore discovered that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express luteinizing hormone, not previously seen in enteroendocrine cells.
2021-03-09 | GSE157694 | GEO
Project description:Proteomic profiling of forty trace samples (20 duodenum cancer samples and 20 gastric cancer samples).
2021-06-16 | PXD026756 |
Project description:Human gastrointestinal epithelia of the esophagus, stomach and duodenum resolved at single-cell resolution
| PRJNA662498 | ENA
Project description:We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas using 32k high-resolution array-based comparative genomic hybridization (aCGH) and 27k oligo gene expression arrays and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-q23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike. Three types of gastroesophageal adenocarcinomas; 7 distal esophageal (EA) tumors, 9 junctional (JA) and 7 proximal stomach cancers (GA) was genomically profiled using tiling 32k BAC-arrays. Two replicates of tumors IDs 1-EA-CGH (replicate 1-EA-CGH-2), 12-EA-CGH (replicate 12-EA-CGH-2) and 18-EA-CGH (replicate 18-EA-CGH-2). Reference samples consist of a pool of male DNA (Promega, Madison, WI, USA).
2010-06-24 | E-GEOD-22524 | biostudies-arrayexpress
Project description:Unpublished single cell RNAseq data from pan-GI integration study from healthy adult donors (20-70 years old; stomach, duodenum, ileum) and control samples from preterm infants (23-31 PCW; small intestine and colon). Details for sample processing can be found in the manuscript.
2024-11-21 | E-MTAB-14050 | biostudies-arrayexpress
Project description:Patients were recruited at the Departments of Abdominal Surgery and Endoscopy of the Hospital do Cancer AC Camargo (São Paulo/Brazil) during a 4-year period (2001 to 2004). All patients signed a pre-informed consent and the study was approved by the internal ethics committee. Tissue samples were either snap frozen in liquid nitrogen (when obtained by surgery) or collected in RNAlaterTM (Ambion®, Austin, Texas USA, when obtained by biopsy). For all samples, diagnosis was confirmed by H&E staining at the time of RNA extraction. Biopsy samples of the esophageal and gastric mucosa obtained by endoscopy had information of the correct anatomical location using a standard diagram. Frozen samples were dissected and only those having at least 70% of tumor cells were processed. A total of 71 samples were analyzed: 39 esophagus and esophagogastric junction samples (9 normal mucosa, 6 esophagitis mucosa, 10 Barrett's mucosa - 4 for the long type and 6 for the short type, and 14 tumor samples of adenocarcinoma) and 32 stomach samples (6 normal body and antrum mucosa, 5 normal cardiac mucosa, 9 intestinal metaplasia mucosa, 7 samples of intestinal type adenocarcinoma and 5 samples of diffuse type carcinoma). For Barrett's samples, diagnosis required evidence of intestinal metaplasia together with tongues or segments of red columnar-appearing epithelium extending upwards from the esophagogastric junction. A long Barrett's esophagus was defined as longer ?3cm and a short Barrett's esophagus by ?3cm of columnar epithelium (Spechler, 2004). The tumor samples of esophagus and esophagogastric junction were not differentiated. For the gastric adenocarcinoma samples were used the Laurén's classification (Laurén, 1965) and the others gastric sample were previously described (Meireles et al, 2003). Keywords: other
2005-05-09 | GSE2444 | GEO
Project description:Forced expression of transcription factors for lineage reprogramming brings hope to cell-based therapy. However, its application is hampered by risks of potential genetic aberrations and tumorigenicity. Using defined small molecules in presence of gastric stromal cells as feeders, we reprogramed human gastric epithelia into induced multipotent endodermal progenitors (hiMEPs) with efficiency of up-to-6%. The hiMEPs expressed genes relative to endodermal lineages but not associating with pluripotency, and could be expanded clonogenically remaining as undifferentiated colonies. Upon induction, hiMEPs were able to give rise to multiple functional endodermal cell types, apart from ectodermal or mesodermal lineages. TGFβ inhibition and particular Wnt signaling activation were crucial in reprogramming process. Collective advantages of availability from donors without age restriction, capabilities in expansion and differentiation, and no concern of tumorigenesis, let hiMEPs have the considerable application potentials on cell therapies of diseases such as liver failure and diabetes, as well as personalized drug-screenings. Human gastric epithelial cells (hGECs) and gastric subepithelial myofibroblasts (GSEMFs) are isolated from human stomach, and human duodenum epithelial cells (hDECs) are isolated from human duodenum. Human Induced multipotent endodermal stem cells (hiMESCs) were reprogrammed from hGECs/hDECs by small molecules with the support of GSEMFs. Definitive endoderm cells (DEs) are derived from human embryonic stem cells by differentiation. Totally, 13 samples including two samples of hDECs, one sample of hGECs, two clones of D-hiMESCs, one clone of G-hiMESCs, four samples of DEs and three samples of GSCs were analyzed using microarray.
2016-07-24 | E-GEOD-71301 | biostudies-arrayexpress
Project description:The upper gastrointestinal tract consisting of the esophagus, stomach and duodenum controls food transport, digestion, nutrient uptake and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly defined their distinct cell types. We identified a quiescent COL17A1high stem/progenitor cell population within the most basal cell layer of the esophagus and detected substantial gene expression differences between identical cell types of the human and mouse stomach. Selective and high expression of BEST4, CFTR, guanylin and uroguanylin identified a new rare cell type in the duodenum, referred to as BCHE cells, which likely mediate high-volume fluid secretion due to continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Previously uncharacterized serotonin-producing enterochromaffin cells in the antral stomach are shown to significantly differ in gene expression from the duodenal enterochromaffin cells. We furthermore discovered that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express the luteinizing hormone, which was not previously seen in enteroendocrine cells.
| EGAS00001004695 | EGA
Project description:Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett’s esophagus have not been resolved in humans. Here, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly revealed that the squamous esophagus and gastric cardia contained cells belonging to common lineages that also included transitional basal progenitor cells; both esophageal and gastric tissues were also related to Barrett's esophagus. Barrett’s esophagus biopsies consisted of multiple clones, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic lesions were initiated by the expansion of a single molecularly aberrant Barrett’s esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the disease trajectory, from its origin to cancer.
2025-01-31 | GSE288235 | GEO