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Series GSE97178 Query DataSets for GSE97178
Status Public on Jun 03, 2021
Title Hybrid stomach-intestinal chromatin states underlie human Barrett’s metaplasia
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design ChIP-Seq on FFPE human tissue obtained on routine clinical endoscopy

Single Cell ATAC-seq on human Barretts metaplasia biopsy, stomach body biopsy and dudenal biopsy.
Contributor(s) Singh H, Ha K, Hornick JL, Madha S, Cejas P, Jajoo K, Singh P, Polak P, Lee H, Shivdasani RA
Citation(s) 34090884
Submission date Mar 29, 2017
Last update date Sep 02, 2021
Contact name Ramesh Shivdasani
Organization name Dana Farber Cancer Institute
Department Medical Oncology
Lab Shivdasani
Street address 450 Brookline Ave. Dana 720D
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (40)
GSM2559141 H3K4me2_ChIPseq [HS5-Barretts]
GSM2559143 H3K4me2_ChIPseq [HS19-Barretts]
GSM2559145 H3K4me2_ChIPseq [HS22-Barretts]
BioProject PRJNA380898
SRA SRP102694

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Supplementary file Size Download File type/resource
GSE97178_RAW.tar 21.8 Gb (http)(custom) TAR (of BED, BW, MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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