Single cell RNA-seq reveals profound transcriptional similarity between Barrett’s oesophagus and oesophageal submucosal glands

Richard Peter Owen, Michael Joseph White, David Tyler Severson, Barbara Braden, Adam Bailey, Robert Goldin, Lai Mun Wang, Carlos Ruiz-Puig, Nicholas David Maynard, Angie Green, Paolo Piazza, David Buck, Mark Ross Middleton, Chris Paul Ponting, Benjamin Schuster-Böckler () and Xin Lu ()
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Richard Peter Owen: University of Oxford
Michael Joseph White: University of Oxford
David Tyler Severson: University of Oxford
Barbara Braden: University of Oxford
Adam Bailey: University of Oxford
Robert Goldin: St Mary’s Hospital, Imperial College
Lai Mun Wang: Oxford University Hospitals NHS Foundation Trust
Carlos Ruiz-Puig: University of Oxford
Nicholas David Maynard: Oxford University Hospitals
Angie Green: University of Oxford
Paolo Piazza: University of Oxford
David Buck: University of Oxford
Mark Ross Middleton: Old Road Campus Research Building, Roosevelt Drive
Chris Paul Ponting: MRC IGMM, University of Edinburgh
Benjamin Schuster-Böckler: University of Oxford
Xin Lu: University of Oxford

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice.

Date: 2018
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DOI: 10.1038/s41467-018-06796-9

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