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

被引：64

作者：

Owen, Richard Peter ^{[1
]}

White, Michael Joseph ^{[1
]}

Severson, David Tyler ^{[1
]}

Braden, Barbara ^{[2
]}

Bailey, Adam ^{[2
]}

Goldin, Robert ^{[3
]}

Wang, Lai Mun ^{[4
]}

Ruiz-Puig, Carlos ^{[1
]}

Maynard, Nicholas David ^{[5
]}

Green, Angie ^{[6
]}

Piazza, Paolo ^{[6
,9
]}

Buck, David ^{[6
]}

Middleton, Mark Ross ^{[7
]}

Ponting, Chris Paul ^{[8
]}

Schuster-Bockler, Benjamin ^{[1
]}

Lu, Xin ^{[1
]}

机构：

[1] Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Med, Oxford OX3 7DQ, England

[2] Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, Oxford OX3 9DU, England

[3] Imperial Coll, St Marys Hosp, Ctr Pathol, London W2 1NY, England

[4] Oxford Univ Hosp NHS Fdn Trust, Dept Pathol, Oxford OX3 9DU, England

[5] Oxford Univ Hosp, Dept Upper GI Surg, Oxford OX3 7LE, England

[6] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[7] Dept Oncol, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England

[8] Univ Edinburgh, MRC, Human Genet Unit, MRC IGMM, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland

[9] Imperial Coll London, Dept Med, Fac Med, London W12 0NN, England

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

STEM-CELLS; SQUAMOUS ISLANDS; INTESTINAL DIFFERENTIATION; METAPLASIA; EXPRESSION; ADENOCARCINOMA; EPITHELIUM; MARKER; CANCER; MODEL;

D O I：

10.1038/s41467-018-06796-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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