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首页> 外文期刊>Nature >Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus
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Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus

机译：鳞状-柱状交界处的过渡基底细胞产生巴雷特食管

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摘要

In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy(1-3), but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown(1-3). In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells(4). On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells(5-8). Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63(+)KRT5(+)KRT7(+)) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63(+)KRT5(+)KRT7(+) basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.
机译：在一些器官系统中，不同类型上皮之间的过渡区是肿瘤前化生和恶性肿瘤的热点（1-3），但这些化生上皮和随后恶性肿瘤的起源细胞仍然未知（1-3）。就巴雷特食管而言，肠上皮化生发生在胃食管连接处，在这里，分层的鳞状上皮转变为简单的柱状细胞（4）。在许多实验模型的基础上，已经提出了几种替代的细胞类型作为该化生的来源，但在所有情况下证据尚无定论：就肠道杯状细胞的存在而言，没有任何模型能够完全模仿Barrett食道（5-） 8）。在这里，我们描述了在小鼠模型中上消化道的鳞状-柱状交界处具有不同基础祖细胞（p63（+）KRT5（+）KRT7（+））的过渡柱状上皮。我们使用多种模型和谱系追踪策略来表明，该鳞状-柱状交界处的基底细胞群可作为过渡上皮祖细胞的来源。在异位表达CDX2时，这些过渡性基础祖细胞分化为肠样上皮（包括杯状细胞），从而复制Barrett的化生。类似的过渡柱状上皮存在于其他小鼠组织的过渡区（包括肛门直肠交界处）以及人类肠道的胃食管交界处。酸性反流性食管炎和多层上皮（被认为是Barrett食管的前体）均以过渡性基础祖细胞的扩张为特征。我们的发现揭示了上消化道上皮中先前未鉴定的过渡区，并提供了证据表明该区中的p63（+）KRT5（+）KRT7（+）基础细胞是多层上皮和Barrett的起源细胞食管。

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  • 来源
    《Nature》 |2017年第7677期|529-533|共5页
  • 作者

    Jiang Ming; Li Haiyan; Zhang Yongchun; Yang Ying; Lu Rong; Liu Kuancan; Lin Sijie; Lan Xiaopeng; Wang Haikun; Wu Han; Zhu Jian; Zhou Zhongren; Xu Jianming; Lee Dong-Kee; Zhang Lanjing; Lee Yuan-Cho; Yuan Jingsong; Abrams Julian A.; Wang Timothy C.; Sepulveda Antonia R.; Wu Qi; Chen Huaiyong; Sun Xin; She Junjun; Chen Xiaoxin; Que Jianwen;

  • 作者单位

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA|Fuzhou Gen Hosp, Inst Lab Med, Fuzhou 350025, Fujian, Peoples R China;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA|Fuzhou Gen Hosp, Inst Lab Med, Fuzhou 350025, Fujian, Peoples R China;

    Fuzhou Gen Hosp, Inst Lab Med, Fuzhou 350025, Fujian, Peoples R China;

    Chinese Acad Sci, Inst Pasteur Shanghai, CAS Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China;

    Ascendas Genom Inc, Zhongshan 529437, Guangdong, Peoples R China;

    Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA;

    Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA;

    Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA|Southwest Med Univ, Inst Canc Med, Sch Basic Med Sci, Luzhou 646000, Sichuan, Peoples R China;

    Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA;

    Univ Med Ctr Princeton Plainsboro, Dept Pathol, Plainsboro, NJ 08536 USA|Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA;

    Columbia Univ, Med Ctr, Dept Radiat Oncol, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Radiat Oncol, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

    Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA;

    Tianjin Med Univ, Haihe Clin Coll, Tianjin Inst Resp Dis, Dept Basic Med, Tianjin 300350, Peoples R China;

    Tianjin Med Univ, Haihe Clin Coll, Tianjin Inst Resp Dis, Dept Basic Med, Tianjin 300350, Peoples R China;

    Tianjin Med Univ, Haihe Clin Coll, Tianjin Inst Resp Dis, Dept Basic Med, Tianjin 300350, Peoples R China;

    Xi An Jiao Tong Univ, Affiliated Hosp 1, Med Coll, Dept Gen Surg, Xian 710061, Shaanxi, Peoples R China;

    North Carolina Cent Univ, Biomed Biotechnol Res Inst, Durham, NC 27707 USA;

    Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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