Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; Vanderbilt Program in Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
Cell Mol Gastroenterol Hepatol. 2024;18(2):101347. doi: 10.1016/j.jcmgh.2024.04.004. Epub 2024 Apr 24.
BACKGROUND & AIM: Telocytes, a recently identified type of subepithelial interstitial cell, have garnered attention for their potential roles in tissue homeostasis and repair. However, their contribution to gastric metaplasia remains unexplored. This study elucidates the role of telocytes in the development of metaplasia within the gastric environment.
To investigate the presence and behavior of telocytes during metaplastic transitions, we used drug-induced acute injury models (using DMP-777 or L635) and a genetically engineered mouse model (Mist1-Kras). Lineage tracing via the Foxl1-CreERT2;R26R-tdTomato mouse model was used to track telocyte migratory dynamics. Immunofluorescence staining was used to identify telocyte markers and evaluate their correlation with metaplasia-related changes.
We confirmed the existence of FOXL1+/PDGFRα+ double-positive telocytes in the stomach's isthmus region. As metaplasia developed, we observed a marked increase in the telocyte population. The distribution of telocytes expanded beyond the isthmus to encompass the entire gland and closely reflected the expansion of the proliferative cell zone. Rather than a general response to mucosal damage, the shift in telocyte distribution was associated with the establishment of a metaplastic cell niche at the gland base. Furthermore, lineage-tracing experiments highlighted the active recruitment of telocytes to the emerging metaplastic cell niche, and we observed expression of Wnt5a, Bmp4, and Bmp7 in PDGFRα+ telocytes.
These results suggest that telocytes contribute to the evolution of a gastric metaplasia niche. The dynamic behavior of these stromal cells, their responsiveness to metaplastic changes, and potential association with Wnt5a, Bmp4, and Bmp7 signaling emphasize the significance of telocytes in tissue adaptation and repair.
近年来发现的一种上皮下间质细胞—— 间质细胞，因其在组织稳态和修复中的潜在作用而备受关注。然而，其在胃化生中的作用仍未被探索。本研究阐明了间质细胞在胃化生发展中的作用。
为了研究间质细胞在化生过程中的存在和行为，我们使用了药物诱导的急性损伤模型（使用 DMP-777 或 L635）和一种基因工程小鼠模型（Mist1-Kras）。通过 Foxl1-CreERT2;R26R-tdTomato 小鼠模型进行谱系追踪，以跟踪间质细胞的迁移动态。免疫荧光染色用于鉴定间质细胞标志物，并评估其与化生相关变化的相关性。
我们证实了 FOXL1+/PDGFRα+双阳性间质细胞在胃峡部区域的存在。随着化生的发展，我们观察到间质细胞数量的显著增加。间质细胞的分布范围扩大到峡部以外，涵盖整个腺体，并紧密反映了增殖细胞区的扩展。这种间质细胞分布的转变不是对黏膜损伤的一般反应，而是与在腺体基部建立化生细胞龛相关。此外，谱系追踪实验突出了间质细胞向新出现的化生细胞龛的主动募集，并且我们观察到 PDGFRα+间质细胞中表达 Wnt5a、Bmp4 和 Bmp7。
这些结果表明间质细胞有助于胃化生龛的演变。这些基质细胞的动态行为、它们对化生变化的反应能力以及与 Wnt5a、Bmp4 和 Bmp7 信号的潜在关联强调了间质细胞在组织适应和修复中的重要性。
