Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage.
Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage.
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DOI：
10.1242/dev.131490
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发表时间：
2016-05-01
期刊：
影响因子：
--
通讯作者：
Garcia MI
中科院分区：
文献类型：
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作者：
Fernandez Vallone V;Leprovots M;Strollo S;Vasile G;Lefort A;Libert F;Vassart G;Garcia MI
在绒毛形成之前衬于上皮的小鼠胎儿肠祖细胞在离体培养时生长为球状体，并表达作为标记物的跨膜糖蛋白Trop2。在这里，我们报告的特征Trop2表达细胞从胎儿前腺胃，生长为不朽的未分化的球体，以及它们与胃的发育和再生的关系。产生胃球体的Trop2+细胞不同于成人腺Lgr5+干细胞，但与胎儿肠球体高度相关。虽然它们共享一个共同的球体签名，肠和胃胎儿球体生成细胞表达器官特异性转录因子，并致力于肠和腺胃分化，分别。Trop2的表达是短暂的腺胃发育过程中，正在失去的腺体形成的发病，而它坚持在鳞状前胃。在稳态下不可检测，Trop2在急性Lgr5+干细胞消融或吲哚美辛诱导的损伤后在腺体中强烈重新表达。这些高度增殖反应性的成人Trop2+细胞表现出与胃胚胎Trop2+细胞相似的转录组，表明成人胃腺上皮再生涉及胎儿遗传程序的部分再表达。总结：Trop2是离体生长的胃胎儿腺上皮的标志物，在成体再生细胞中损伤后与部分胎儿样遗传程序一起重新表达。
Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2+ cells generating gastric spheroids differed from adult glandular Lgr5+ stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5+ stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2+ cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2+ cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program. Summary: Trop2, a marker of gastric fetal glandular epithelium grown ex vivo, is re-expressed upon injury in adult regenerative cells together with a partial fetal-like genetic program.