Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa.
Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa.
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DOI：
10.1136/gutjnl-2021-325310
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发表时间：
2022-06
期刊：
影响因子：
24.5
通讯作者：
Choi E
中科院分区：
文献类型：
--
作者：
Caldwell B;Meyer AR;Weis JA;Engevik AC;Choi E
化生由响应损伤的分化细胞类型引起，并且被认为是许多癌症的前兆。异质性细胞谱系存在于对损伤有反应的修复性化生粘膜中，包括小凹细胞、增殖细胞和痉挛性多肽表达化生（SPEM）细胞（一种关键的化生细胞群）。酶原分泌主细胞是胃粘膜中的长寿细胞，并已被认为是SPEM细胞的起源;然而，一个相互矛盾的范式已提出峡部祖细胞作为SPEM的起源。胃内因子（GIF）是一种胃组织特异性基因，其蛋白表达仅限于成熟的小鼠主细胞。我们产生了一种新的主细胞特异性驱动小鼠等位基因，GIF-rtTA。GIF-GFP报告小鼠用于验证GIF-rtTA驱动子在主细胞中的特异性。使用GIF-Cre-RnTnG小鼠在体内平衡和急性化生发展期间进行谱系追踪。L 635处理用于诱导急性粘膜损伤，并对各种胃谱系标志物进行共免疫荧光染色。我们证明，在急性粘膜损伤后的化生过程中，成熟的主细胞，而不是峡部祖细胞，是SPEM细胞的主要来源。此外，我们在主细胞中GFP标记后1年观察到长期标记保留的主细胞。然而，只有一个非常小的子集的长期标记保留的主细胞显示重编程能力的稳态。与此相反，我们确定了主细胞起源的SPEM细胞，作为对急性粘膜损伤的反应，有助于小凹细胞增生内的谱系。我们的研究提供了关键的证据，细胞可塑性和谱系的贡献，从分化的胃主细胞在急性化生的发展。
Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM. Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers. We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury. Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1016/j.jcmgh.2016.11.001
发表时间：
2017-01
影响因子：
7.2
作者：
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通讯作者：
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影响因子：
50.3
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